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Biomedical subjects

S M Smith

Publications and source records attributed to S M Smith.

At least 19 recordsLinked to original sources
PubMed2006

Cerebral critical closing pressure estimation from Finapres and arterial blood pressure measurements in the aorta.

Estimates of cerebral critical closing pressure (CrCP) and resistance-area product (RAP) are often derived using noninvasive measurements of arterial blood pressure (ABP) in the finger, but the errors introduced by this approach, in relation to intra-vascular measurements of ABP, are not known. Continuous recordings of ABP (Finapres and solid-state catheter-tip transducer in the ascending aorta), cerebral blood flow velocity (CBFV, bilateral Doppler), ECG and transcutaneous CO(2) were performed following coronary catheterization. CrCP and RAP were calculated for each of 12,784 cardiac cycles from 27 subjects using the classical linear regression (LR) of the instantaneous CBFV-ABP relationship and also the first harmonic (H(1)) of the Fourier transform. There was a better agreement between LR and H(1) for the aortic measurements than for the Finapres (p < 0.000,01). For LR there were no significant differences for either CrCP or RAP due to the source of ABP measurement, but for H(1) the differences were highly significant (p < 0.000,03). The coherence functions between either CrCP or RAP values calculated with aortic pressure (input) or the Finapres (output) were significantly higher for H(1) than for LR for most harmonics below 0.2 Hz. When using the Finapres to estimate CrCP and RAP values, the LR method produces similar results to intra-arterial measurements of ABP for time-averaged values, but H(1) should be preferred in applications analysing beat-to-beat changes in these parameters.

Airway Obstruction↗
PubMed2006

HPLC-NMR with severe column overloading: fast-track metabolite identification in urine and bile samples from rat and dog treated with [14C]-ZD6126.

The subject of this study was the determination of the major urinary and biliary metabolites of [(14)C]-ZD6126 following i.v. administration to female and male bile duct cannulated rats at 10 mg/kg and 20 mg/kg, respectively, and male bile duct cannulated dogs at 6 mg/kg by HPLC-NMR spectroscopy. ZD6126 is a phosphorylated pro-drug, which is rapidly hydrolysed to the active metabolite, ZD6126 phenol. The results presented here demonstrate that [(14)C]-ZD6126 phenol is subsequently metabolised extensively by male dogs and both, male and female rats. Recovery of the dose in bile and urine was determined utilising the radiolabel, revealing biliary excretion as the major route of excretion (93%) in dog, with the majority of the radioactivity recovered in both biofluids in the first 6 h. In the rat, greater than 92% recovery was obtained within the first 24 h. The major route of excretion was via the bile 51-93% within the first 12 h. The administered phosphorylated pro-drug was not observed in any of the excreta samples. Metabolite profiles of bile and urine samples were determined by high performance liquid chromatography with radiochemical detection (HPLC-RAD), which revealed a number of radiolabelled components in each of the biofluids. The individual metabolites were subsequently identified by HPLC-NMR spectroscopy and HPLC-MS. In the male dog, the major component in urine and bile was the [(14)C]-ZD6126 phenol glucuronide, which accounted for 3% and 77% of the dose, respectively. [(14)C]-ZD6126 phenol was observed in urine at 1% of dose, but was not observed in bile. A sulphate conjugate of demethylated [(14)C]-ZD6126 phenol was identified in bile by HPLC-NMR and confirmed by HPLC-MS. In the rat, the bile contained two major radiolabelled components. One was identified as the [(14)C]-ZD6126 phenol glucuronide, the other as a glucuronide conjugate of demethylated [(14)C]-ZD6126 phenol. However, a marked difference in the proportions of these two components was observed between male and female rats, either due to a sex difference in metabolism or a difference in dose level. The glucuronide conjugate of the demethylated [(14)C]-ZD6126 phenol was present at higher concentration in the bile of male rats (4-34%), while the phenol glucuronide was present at higher concentration in the bile of female rats (8-70%) over a 0-6 h collection period. A third component was only observed in the bile samples (0-6 h and 6-12 h) of male rats. This was identified as being the same sulphate conjugate of demethylated [(14)C]-ZD6126 phenol as the one observed in dog bile. The rat urines contained two main metabolites in greatly varying concentrations, namely the demethylated [(14)C]-ZD6126 phenol glucuronide and the glucuronide of [(14)C]-ZD6126 phenol. Again, the differences in relative amounts between male and female rats were observed, the major metabolite in the urines from male rats being the demethylated [(14)C]-ZD6126 phenol (0-17% in 0-24 h), whilst the phenol glucuronide, accounting for 0.5-50% of the dose over 0-24 h, was the major metabolite in females. Methanolic extracts of the pooled biofluid samples were submitted for HPLC-NMR for the quick identification of the major metabolites. Following a single injection of the equivalent of 6-28 ml of the biofluids directly onto the HPLC-column with minimal sample preparation, the metabolites could be largely successfully isolated. Despite severe column overloading, the major metabolites of [(14)C]-ZD6126 could be positively identified, and the results are presented in this paper.

Animals↗
PubMed2006

Consistent resting-state networks across healthy subjects.

Functional MRI (fMRI) can be applied to study the functional connectivity of the human brain. It has been suggested that fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain, representing the state of the human brain in the absence of goal-directed neuronal action and external input, and that these slow fluctuations correspond to functionally relevant resting-state networks. Several studies on resting fMRI have been conducted, reporting an apparent similarity between the identified patterns. The spatial consistency of these resting patterns, however, has not yet been evaluated and quantified. In this study, we apply a data analysis approach called tensor probabilistic independent component analysis to resting-state fMRI data to find coherencies that are consistent across subjects and sessions. We characterize and quantify the consistency of these effects by using a bootstrapping approach, and we estimate the BOLD amplitude modulation as well as the voxel-wise cross-subject variation. The analysis found 10 patterns with potential functional relevance, consisting of regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the so-called default-mode network, each with BOLD signal changes up to 3%. In general, areas with a high mean percentage BOLD signal are consistent and show the least variation around the mean. These findings show that the baseline activity of the brain is consistent across subjects exhibiting significant temporal dynamics, with percentage BOLD signal change comparable with the signal changes found in task-related experiments.

Brain↗
PubMed2006

Consensus on diabetes management in primary care.

Diabetes management in Irish Primary Care is in the early stages of development. This study used a Delphi technique with a panel of experts working in diabetes in primary care in order to reach a consensus on its future development. There was strong agreement on the need for multidisciplinary professional advocacy to improve services for people with diabetes. The panel indicated a preference for the development of shared models of care and emphasised the importance of research, audit and professional education. The results of this study can be used by health planners to develop services in a way that reflects the experience and opinion of those working as experts in the field of primary care diabetes.

Delphi Technique↗
PubMed2005

A consistent relationship between local white matter architecture and functional specialisation in medial frontal cortex.

Functionally significant landmarks in the brain do not necessarily align with local sulcal and gyral architecture in a manner that is consistent across individuals. However, the functional specialisation underlying these landmarks is strongly constrained by the connectional architecture of the region. Here, we explore this relationship in the supplementary motor area (SMA) and pre-SMA in the medial frontal cortex of the human brain. Using diffusion tensor, conventional and functional MR imaging, we find that the location of the functional boundary between SMA and preSMA is more consistent with respect to specific features of the local white matter as it approaches neocortex than with respect to the local gyral and sulcal anatomy in the region.

Adult↗
PubMed2005

fMRI resting state networks define distinct modes of long-distance interactions in the human brain.

Functional magnetic resonance imaging (fMRI) studies of the human brain have suggested that low-frequency fluctuations in resting fMRI data collected using blood oxygen level dependent (BOLD) contrast correspond to functionally relevant resting state networks (RSNs). Whether the fluctuations of resting fMRI signal in RSNs are a direct consequence of neocortical neuronal activity or are low-frequency artifacts due to other physiological processes (e.g., autonomically driven fluctuations in cerebral blood flow) is uncertain. In order to investigate further these fluctuations, we have characterized their spatial and temporal properties using probabilistic independent component analysis (PICA), a robust approach to RSN identification. Here, we provide evidence that: i. RSNs are not caused by signal artifacts due to low sampling rate (aliasing); ii. they are localized primarily to the cerebral cortex; iii. similar RSNs also can be identified in perfusion fMRI data; and iv. at least 5 distinct RSN patterns are reproducible across different subjects. The RSNs appear to reflect "default" interactions related to functional networks related to those recruited by specific types of cognitive processes. RSNs are a major source of non-modeled signal in BOLD fMRI data, so a full understanding of their dynamics will improve the interpretation of functional brain imaging studies more generally. Because RSNs reflect interactions in cognitively relevant functional networks, they offer a new approach to the characterization of state changes with pathology and the effects of drugs.

Adult↗
PubMed2005

Removal of FMRI environment artifacts from EEG data using optimal basis sets.

The combination of functional magnetic resonance imaging (FMRI) and electroencephalography (EEG) has received much recent attention, since it potentially offers a new tool for neuroscientists that makes simultaneous use of the strengths of the two modalities. However, EEG data collected in such experiments suffer from two kinds of artifact. First, gradient artifacts are caused by the switching of magnetic gradients during FMRI. Second, ballistocardiographic (BCG) artifacts related to cardiac activities further contaminate the EEG data. Here we present new methods to remove both kinds of artifact. The methods are based primarily on the idea that temporal variations in the artifacts can be captured by performing temporal principal component analysis (PCA), which leads to the identification of a set of basis functions which describe the temporal variations in the artifacts. These basis functions are then fitted to, and subtracted from, EEG data to produce artifact-free results. In addition, we also describe a robust algorithm for the accurate detection of heart beat peaks from poor quality electrocardiographic (ECG) data that are collected for the purpose of BCG artifact removal. The methods are tested and are shown to give superior results to existing methods. The methods also demonstrate the feasibility of simultaneous EEG/FMRI experiments using the relatively low EEG sampling frequency of 2048 Hz.

Algorithms↗
PubMed2005

Amino acid supplementation alters bone metabolism during simulated weightlessness.

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Adult↗
PubMed2005

Tensorial extensions of independent component analysis for multisubject FMRI analysis.

We discuss model-free analysis of multisubject or multisession FMRI data by extending the single-session probabilistic independent component analysis model (PICA; Beckmann and Smith, 2004. IEEE Trans. on Medical Imaging, 23 (2) 137-152) to higher dimensions. This results in a three-way decomposition that represents the different signals and artefacts present in the data in terms of their temporal, spatial, and subject-dependent variations. The technique is derived from and compared with parallel factor analysis (PARAFAC; Harshman and Lundy, 1984. In Research methods for multimode data analysis, chapter 5, pages 122-215. Praeger, New York). Using simulated data as well as data from multisession and multisubject FMRI studies we demonstrate that the tensor PICA approach is able to efficiently and accurately extract signals of interest in the spatial, temporal, and subject/session domain. The final decompositions improve upon PARAFAC results in terms of greater accuracy, reduced interference between the different estimated sources (reduced cross-talk), robustness (against deviations of the data from modeling assumptions and against overfitting), and computational speed. On real FMRI 'activation' data, the tensor PICA approach is able to extract plausible activation maps, time courses, and session/subject modes as well as provide a rich description of additional processes of interest such as image artefacts or secondary activation patterns. The resulting data decomposition gives simple and useful representations of multisubject/multisession FMRI data that can aid the interpretation and optimization of group FMRI studies beyond what can be achieved using model-based analysis techniques.

Artifacts↗
PubMed2004

Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex.

A fundamental issue in neuroscience is the relation between structure and function. However, gross landmarks do not correspond well to microstructural borders and cytoarchitecture cannot be visualized in a living brain used for functional studies. Here, we used diffusion-weighted and functional MRI to test structure-function relations directly. Distinct neocortical regions were defined as volumes having similar connectivity profiles and borders identified where connectivity changed. Without using prior information, we found an abrupt profile change where the border between supplementary motor area (SMA) and pre-SMA is expected. Consistent with this anatomical assignment, putative SMA and pre-SMA connected to motor and prefrontal regions, respectively. Excellent spatial correlations were found between volumes defined by using connectivity alone and volumes activated during tasks designed to involve SMA or pre-SMA selectively. This finding demonstrates a strong relationship between structure and function in medial frontal cortex and offers a strategy for testing such correspondences elsewhere in the brain.

Adult↗
PubMed2004

Biological soil crusts of sand dunes in Cape Cod National Seashore, Massachusetts, USA.

Biological soil crusts cover hundreds of hectares of sand dunes at the northern tip of Cape Cod National Seashore (Massachusetts, USA). Although the presence of crusts in this habitat has long been recognized, neither the organisms nor their ecological roles have been described. In this study, we report on the microbial community composition of crusts from this region and describe several of their physical and chemical attributes that bear on their environmental role. Microscopic and molecular analyses revealed that eukaryotic green algae belonging to the genera Klebsormidium or Geminella formed the bulk of the material sampled. Phylogenetic reconstruction of partial 16S rDNA sequences obtained from denaturing gradient gel electrophoresis (DGGE) fingerprints also revealed the presence of bacterial populations related to the subclass of the Proteobacteria, the newly described phylum Geothrix/ Holophaga/ Acidobacterium, the Cytophaga/ Flavobacterium/ Bacteroides group, and spirochetes. The presence of these crusts had significant effects on the hydric properties and nutrient status of the natural substrate. Although biological soil crusts are known to occur in dune environments around the world, this study enhances our knowledge of their geographic distribution and suggests a potential ecological role for crust communities in this landscape.

Bacteria↗
PubMed2004

Variability of collagen crosslinks: impact of sample collection period.

Because of the variability of collagen crosslinks, their use as markers for bone resorption is often criticized. We hypothesized that the variability could be reduced by collecting urine for 24 hours (or longer) instead of using single voids, and by not normalizing to creatinine. Urine samples were collected from 22 healthy subjects during two or more 24-hour periods. Each 24-hour pool and each 2nd void of the day were analyzed for N-telopeptide (NTX), pyridinium (PYD), and deoxypyridinoline (DPD) crosslinks. Data were analyzed by using linear regression. For NTX, R2 for the two, 2nd-void samples (n = 38) was 0.55, whereas R2 for the two 24-hour pools was 0.51 or 0.52, expressed per day or per creatinine. For PYD and DPD, R2 for the 2nd-void samples was 0.26 and 0.18, R2 for the 24-hour pools expressed per day was 0.58 and 0.74, and R2 for the 24-hour pools expressed per creatinine was 0.65 and 0.76, respectively. Regression of the 2nd void and the corresponding 24-hour pool, expressed per day, yielded R2 = 0.19, 0.19, and 0.08, for NTX, PYD, and DPD, respectively (n = 76 each). For the 2nd-void sample and its corresponding 24-hour pool, expressed per creatinine, R2 = 0.24, 0.33, and 0.08, respectively. In a separate study, the coefficient of variation for NTX was reduced (P < 0.05) when data from more than one 24-hour collection were combined. Thus, the variability inherent in crosslink determinations can be reduced by collecting urine for longer periods. In research studies, the high variability of single-void collections, compounded by creatinine normalization, may alter or obscure findings.

Adult↗
PubMed2004

Relating neocortical pathology to disability progression in multiple sclerosis using MRI.

Cortical grey matter (cGM) develops a substantial burden of pathology in multiple sclerosis (MS). Previous cross-sectional studies have suggested a relationship between measures of cortical atrophy and disability. Our objective was to develop a method for automatically measuring the apparent cGM thickness as well as the integrity of the interface between cGM and subcortical white matter (GM/WM) both globally and regionally on T(1)-weighted MRI, and use this method in a longitudinal investigation of how these measures differed between patients with stable MS and patients with progressing disability. Measurements were made over the whole brain and for anatomically specified cortical regions, both cross-sectionally at baseline and longitudinally on two MRI scans performed on average 1 year apart. We found a higher average rate of apparent loss of cGM thickness across the whole brain in the group that progressed over the interscan interval compared to the group that remained stable (progressing = -3.13 +/- 2.88%/year, stable = 0.06 +/- 2.31%/year, P = 0.002). This difference was detected with regional measures in parietal and precentral cortex. In contrast, change in the GM/WM interface integrity did not show detectable regional differences, although the group of MS patients whose disability progressed showed a significant decrease in GM/WM interface integrity compared to the stable group (P = 0.003). Regional measures of apparent loss of cGM thickness enhance sensitivity to cortical pathological changes. A measure of integrity offers a new index of disease-associated cortical changes at the GM/WM interface. The results suggest that progression of disability in MS is associated with the progression of MRI-detectable cortical pathology.

Adult↗
PubMed2004

Provision of oncology services in remote rural areas: a Scottish perspective.

There is a paucity of research into rural health care services. In particular little is known about the provision of specialist cancer services for patients who live in remote rural areas of the UK. This study set out to investigate current models of medical and clinical oncology care in Scotland. A national survey with key health professionals was conducted to identify rural oncology schemes currently in operation. Detailed quantitative data about the schemes together with qualitative data on how health professionals view current models of care were collected by a computer-assisted telephone survey. Schemes that currently provide outpatient and chemotherapy oncology services for remote rural patients fell into three categories: central clinics (5); shared care outreach clinics with chemotherapy provision (11); and shared care outreach clinics without chemotherapy provision (7). All radiotherapy was conducted at central clinics (5). Widely varying practices in delivery of cancer care were found across the country. The main issues for professionals about current models of care involved expertise, travelling and accessibility (for patients), communication and expansion of the rural service. Nation-wide consistency in cancer care has still to be achieved. Travelling for treatment was seen to take its toll on all patients but particularly for the very remote, elderly and poor. Most professionals believe that an expansion of rural services would be of benefit to these patients. It is clear, however, that the proper infrastructure needs to be in place in terms of local expertise, ensured quality of care, and good communication links with cancer centres before this could happen.

Health Services Accessibility↗
PubMed2004

Resistance exercise as a countermeasure to disuse-induced bone loss.

During spaceflight, skeletal unloading results in loss of bone mineral density (BMD). This occurs primarily in the spine and lower body regions. This loss of skeletal mass could prove hazardous to astronauts on flights of long duration. In this study, intense resistance exercise was used to test whether a training regimen would prevent the loss of BMD that accompanies disuse. Nine subjects (5 men, 4 women) participated in a supine maximal resistance exercise training program during 17 wk of horizontal bed rest. These subjects were compared with 18 control subjects (13 men, 5 women) who followed the same bed rest protocol without exercise. Determination of treatment effect was based on measures of BMD, bone metabolism markers, and calcium balance obtained before, during, and after bed rest. Exercisers and controls had significantly (P < 0.05) different means, represented by the respective following percent changes: lumbar spine BMD, +3% vs. -1%; total hip BMD, +1% vs. -3%; calcaneus BMD, +1% vs. -9%; pelvis BMD, -0.5% vs. -3%; total body BMD, 0% vs. -1%; bone-specific alkaline phosphatase, +64% vs. 0%; alkaline phosphatase, +31% vs. +5%; osteocalcin, +43% vs. +10%; 1,25 dihydroxyvitamin D, +12% vs. -15%; parathyroid hormone intact molecule, +18% vs. -25%; and serum and ionized calcium, -1% vs. +1%. The difference in net calcium balance was also significant (+21 mg/day vs. -199 mg/day, exercise vs. control). The gastrocnemius and soleus muscle volumes decreased significantly in the exercise group, but the loss was significantly less than observed in the control group. The results indicate that resistance exercise had a positive treatment effect and thus might be useful as a countermeasure to prevent the deleterious skeletal changes associated with long-duration spaceflight.

Adult↗