Biomedical subjects

Robert Turner

Publications and source records attributed to Robert Turner.

At least 19 recordsLinked to original sources

PubMed2025

Evaluating 12 automated, whole-genome sequencing analysis pipelines for Mycobacterium tuberculosis complex: a comparative study.

BACKGROUND: Reliance on complex, custom-built bioinformatics pipelines is a barrier to the implementation of whole-genome sequencing (WGS) of Mycobacterium tuberculosis in high-burden settings in some low-income and middle-income countries (LMICs). Automated analysis pipelines could address this inequity in access to WGS-based diagnostics and surveillance. This study aimed to systematically evaluate the performance and usability of publicly available WGS pipelines for M tuberculosis. METHODS: We identified automated M tuberculosis WGS analysis pipelines through searches of PubMed and GitHub from database inception up to Aug 31, 2024. Accuracy, cost, accessibility, and scalability were assessed for each pipeline. We evaluated the accuracy of genotypic drug susceptibility testing (gDST) using publicly available sequences with phenotypic susceptibility data for 12 antituberculosis drugs. We estimated pooled sensitivity and specificity for each pipeline, across all drugs, by conducting a bivariate meta-analysis, with random effects representing between-drug variability. Lineage classifications were compared, and a previously epidemiologically well-characterised dataset was used to compare measures of genomic relatedness. FINDINGS: Among 28 candidate pipelines, 16 were excluded as they were unmaintained and inexecutable. 12 pipelines (11 compatible with Illumina and four compatible with Nanopore), all free to use, were included for evaluation. Six pipelines processed and stored data remotely, but for five of these six, scalability was limited by the need to upload sequences through web portals. For local processing pipelines, scalability was dependent on substantial local computational resources, data storage capacity, and command-line interfaces that limited user-friendliness. Only one of six remote-processing pipelines removed human DNA sequences before server upload. gDST was similarly accurate across ten of 11 Illumina-compatible pipelines and three of four Nanopore-compatible pipelines. All pipelines classified the main lineages consistently, although there were differences at sublineage resolution. Outputs from three of four pipelines reporting genomic relatedness were compatible with commonly cited single nucleotide polymorphism difference thresholds. INTERPRETATION: Numerous automated analysis pipelines capable of enhancing equity in M tuberculosis WGS are available. Given the overall similarities between the pipelines evaluated in this study in terms of gDST performance, lineage classification, and genomic relatedness inference, non-functional attributes such as availability, accessibility, scalability, and privacy could represent the point of difference for prospective users in LMICs with a high burden of tuberculosis. FUNDING: The Rhodes Trust, Wellcome, Ellison Institute of Technology, and the UK National Institute for Health and Care Research Oxford Biomedical Research Centre.

Mycobacterium tuberculosis↗

PubMed2006

Improving whole brain structural MRI at 4.7 Tesla using 4 irregularly shaped receiver coils.

Both higher magnetic field strengths (> or =3 T) and multiple receiver "array coils" can provide increased signal-to-noise ratio (SNR) for MRI. This increase in SNR can be used to obtain images with higher resolution, enabling better visualisation of structures within the human brain. However, high field strength systems also suffer from increased B(1) non-uniformity and increased power deposition, reaching specific absorption rate (SAR) limits more quickly. For these problems to be mitigated, a careful choice of both the pulse sequence design and transmit RF coil is required. This paper describes the use of a prototype array coil consisting of 4 irregularly shaped coils within a standard configuration for neuroimaging at 4.7 T (a head transmit/receive volume coil to minimise SAR and a head gradient insert for maximum gradient performance). With a fast spin echo (FSE) pulse sequence optimised for 4.7 T, this provides dramatically increased quality and resolution over a large brain volume. Using the array coil, a SNR improvement relative to the volume coil of 1-1.5 times in central brain areas and 2-3 times in cortical regions was obtained. Array coil images with a resolution of 352 x 352 x 2000 mum had a SNR of 16.0 to 26.2 in central regions and 19.9 to 34.8 in cortical areas. Such images easily demonstrate cortical myeloarchitecture, while still covering most of the brain in a approximately 12 min scan.

Algorithms↗

PubMed2006

BOLD correlates of EMG spectral density in cortical myoclonus: description of method and case report.

The recording of electrophysiological data during BOLD fMRI is highly challenging but provides the opportunity to develop a more thorough account of brain function than either modality alone. To develop new techniques in this area has often required the study of pathological electrophysiological measures because such measures can be unusually strong (e.g., epileptic EEG spikes) and hence more easily detectable during fMRI than weaker normal phenomena. In this paper, we have studied pathologically strong EMG signals in a patient with cortical myoclonus. First, we studied the patient outside of scanning: The pathological corticospinal drive to muscle was concentrated over 6-30 Hz so that EMG components at higher frequency could be used to control for non-corticospinal contributions to the EMG during scanning. Additionally, there was very strong EMG-EMG and EMG-EEG coherence in this frequency band. Furthermore, analysis of spectral phase showed that this exaggerated coherence was produced by efferent drive from brain to muscle. Hence, the exaggerated peak in distal muscle EMG power spectrum reflected brain activity producing the efferent drive. Subsequently, we modified equipment and data analysis techniques previously developed for simultaneous EEG-fMRI to record polychannel EMG from distal upper limbs during simultaneous BOLD fMRI. After artefact reduction, the EMG recorded during fMRI retained the essential frequency and phase characteristics of EMG recorded outside of scanning. The BOLD signal was significantly correlated with time-varying 6- to 30-Hz power in a frontoparietal network compatible with the neurophysiological characteristics of our patient and compatible with prior hypotheses explaining the origin of cortical myoclonus.

Adult↗

PubMed2006

Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitors.

Structure-based design, synthesis, and X-ray structure of protein-ligand complexes of memapsin 2 are described. The inhibitors are designed specifically to interact with S2- and S3-active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 6 has exhibited exceedingly potent inhibitory activity against memapsin 2 and selectivity over memapsin 1 (>3800-fold) and cathepsin D (>2500-fold). A protein-ligand crystal structure revealed cooperative interactions in the S2- and S3-active sites of memapsin 2. These interactions may serve as an important guide to design selectivity over memapsin 1 and cathepsin D.

Amyloid Precursor Protein Secretases↗

PubMed2006

Song and speech: brain regions involved with perception and covert production.

This 3-T fMRI study investigates brain regions similarly and differentially involved with listening and covert production of singing relative to speech. Given the greater use of auditory-motor self-monitoring and imagery with respect to consonance in singing, brain regions involved with these processes are predicted to be differentially active for singing more than for speech. The stimuli consisted of six Japanese songs. A block design was employed in which the tasks for the subject were to listen passively to singing of the song lyrics, passively listen to speaking of the song lyrics, covertly sing the song lyrics visually presented, covertly speak the song lyrics visually presented, and to rest. The conjunction of passive listening and covert production tasks used in this study allow for general neural processes underlying both perception and production to be discerned that are not exclusively a result of stimulus induced auditory processing nor to low level articulatory motor control. Brain regions involved with both perception and production for singing as well as speech were found to include the left planum temporale/superior temporal parietal region, as well as left and right premotor cortex, lateral aspect of the VI lobule of posterior cerebellum, anterior superior temporal gyrus, and planum polare. Greater activity for the singing over the speech condition for both the listening and covert production tasks was found in the right planum temporale. Greater activity in brain regions involved with consonance, orbitofrontal cortex (listening task), subcallosal cingulate (covert production task) were also present for singing over speech. The results are consistent with the PT mediating representational transformation across auditory and motor domains in response to consonance for singing over that of speech. Hemispheric laterality was assessed by paired t tests between active voxels in the contrast of interest relative to the left-right flipped contrast of interest calculated from images normalized to the left-right reflected template. Consistent with some hypotheses regarding hemispheric specialization, a pattern of differential laterality for speech over singing (both covert production and listening tasks) occurs in the left temporal lobe, whereas, singing over speech (listening task only) occurs in right temporal lobe.

Adult↗

PubMed2006

Transient monoclonal gammopathy in a patient with Bartonella quintana endocarditis.

Monoclonal gammopathy has been reported rarely in association with infectious diseases. Viral infection has been the most frequently reported. We report a case of Bartonella quintana endocarditis in a 45-year-old homeless male associated with a monoclonal IgG kappa gammopathy. The gammopathy disappeared after 8 months of antibiotics while the Bartonella antibody titre was decreasing. This correlation suggests a causative role for B. quintana for the monoclonal gammopathy. To the best of our knowledge, this the first report of monoclonal gammopathy in the course of B. quintana infection.

Anti-Bacterial Agents↗

PubMed2006

Cerebral vascular response to hypercapnia: determination with perfusion MRI at 1.5 and 3.0 Tesla using a pulsed arterial spin labeling technique.

PURPOSE: To compare the quantification of cerebral blood flow (CBF) at 1.5 and 3.0 Tesla, under normo- and hypercapnia, and to determine the cerebral vascular response (CVR) of gray matter (GM) to hypercapnia, a pulsed arterial spin labeling technique was used. Additionally, to improve GM CBF quantification a high-resolution GM-mask was applied. MATERIALS AND METHODS: CBF was determined with the QUIPSS II with thin slice TI1 periodic saturation (Q2TIPS) sequence at 1.5 and 3.0 Tesla in the same group of eight subjects, both under normocapnia and hypercapnia. Absolute GM-CBF maps were calculated using a GM-mask obtained from a high-resolution structural scan by segmentation. The CVR to hypercapnia was derived from the quantitative GM-CBF maps. RESULTS: For both field strengths, the GM-CBF was significantly higher under hypercapnia compared to normocapnia. For both conditions, there was no significant difference of GM-CBF for 1.5 and 3.0 Tesla; the same applies to the CVR, which was 4.3 and 4.5%/mmHg at 1.5 and 3.0 Tesla, respectively. CONCLUSION: The method presented allows for the quantification of CBF and CVR in GM at the common clinical field strengths of 1.5 and 3.0 Tesla and could therefore be a useful tool to study these parameters under physiological and pathophysiological conditions.

Adult↗

PubMed2005

Breast implant infection with Mycobacterium fortuitum group: report of case and review.

There has been a marked increase in the frequency with which breast prosthesis are being used, both for reconstructive and cosmetic purposes. Although breast implant-related infections are uncommon, they are typically caused by bacterial skin flora, specifically Staphylococcus aureus and the coagulase negative staphylococci. There have been infrequent reports of breast implant infection caused by the atypical mycobacteria. This report summarizes the case of a young female who underwent augmentation mammoplasty who presented shortly thereafter with clinical evidence of an infected breast prosthesis. Despite a protracted course of empiric antibiotic therapy and multiple surgical interventions, she failed to improve. Additional microbiologic investigations allowed for a diagnosis of Mycobacterium fortuitum group breast implant infection to be established. A prolonged course of anti-mycobacterial therapy, based upon susceptibility results, allowed for eradication of the infection and subsequent successful re-implantation of the prosthesis.

Adult↗

PubMed2005

3D MDEFT imaging of the human brain at 4.7 T with reduced sensitivity to radiofrequency inhomogeneity.

A modification to the 3D modified driven equilibrium Fourier transform (MDEFT) imaging technique is proposed that reduces its sensitivity to RF inhomogeneity. This is especially important at high field strengths where RF focusing effects exacerbate B(1) inhomogeneity, causing significant signal nonuniformity in the images. The adiabatic inversion pulse used during the preparation period of the MDEFT sequence is replaced by a hard (nonadiabatic) pulse with a nominal flip angle of 130 degrees. The spatial inhomogeneity of the hard pulse preparation compensates for the inhomogeneity of the excitation pulses. Uniform signal intensity is obtained for a wide range of B(1) amplitudes and the high CNR characteristic of MDEFT is retained. The new approach was validated by numerical simulations and successfully applied to human brain imaging at 4.7 T, resulting in high-quality T(1)-weighted images of the whole human brain at high field strength with uniform signal intensity and contrast, despite the presence of significant RF inhomogeneity.

Brain Mapping↗

PubMed2005

Selective averaging for the diffusion tensor measurement.

The multishot echo planar imaging sequence was often used in the high-resolution diffusion measurements. However, it is susceptible to motion artifacts because of the requirements of combining the raw data from different acquisitions into one complete k-space data set. Conventional solutions used cardiac gating but greatly extended the total acquisition time. Here we propose a selective averaging algorithm based on the information in the navigator echoes. The data were sampled continuously without cardiac gating. Contributions contaminated by motion were detected by a thresholding algorithm and were discarded during postprocessing. The data were then averaged in the modulus or complex format. Diffusion tensor imaging (DTI) data with isotropic spatial resolution were acquired in phantom as well as from two normal volunteers. The information in the navigator echoes proved to be a good indicator for the extent of motion contamination. Differences were noticed between modulus and complex averaging in DTI quantification, but both showed reduced artifact and improved signal-to-noise ratio.

Adult↗

PubMed2004

Model of local temperature changes in brain upon functional activation.

Experimental results for changes in brain temperature during functional activation show large variations. It is, therefore, desirable to develop a careful numerical model for such changes. Here, a three-dimensional model of temperature in the human head using the bioheat equation, which includes effects of metabolism, perfusion, and thermal conduction, is employed to examine potential temperature changes due to functional activation in brain. It is found that, depending on location in brain and corresponding baseline temperature relative to blood temperature, temperature may increase or decrease on activation and concomitant increases in perfusion and rate of metabolism. Changes in perfusion are generally seen to have a greater effect on temperature than are changes in metabolism, and hence active brain is predicted to approach blood temperature from its initial temperature. All calculated changes in temperature for reasonable physiological parameters have magnitudes <0.12 degrees C and are well within the range reported in recent experimental studies involving human subjects.

Body Temperature↗

PubMed2004

3D DT-MRI using a reduced-FOV approach and saturation pulses.

Diffusion tensor imaging (DTI) can provide vital insights into brain connectivity, and may become an important tool for the diagnosis and treatment of neurological disease. However, DTI's intrinsic low signal-to-noise ratio (SNR) and vulnerability to ghosting artifacts can result in poor image quality with low spatial resolution, which limits its clinical applications. In this study, a new double-shot EPI sequence (half-FOV EPI) with high spatial resolution was developed. This method enables DT measurements to be obtained with high isotropic spatial resolution and whole-brain coverage. To avoid ghosting artifacts, the data are combined in image space rather than in k-space.

Adult↗

PubMed2004

High-resolution fast spin echo imaging of the human brain at 4.7 T: implementation and sequence characteristics.

In this work, a number of important issues associated with fast spin echo (FSE) imaging of the human brain at 4.7 T are addressed. It is shown that FSE enables the acquisition of images with high resolution and good tissue contrast throughout the brain at high field strength. By employing an echo spacing (ES) of 22 ms, one can use large flip angle refocusing pulses (162 degrees ) and a low acquisition bandwidth (50 kHz) to maximize the signal-to-noise ratio (SNR). A new method of phase encode (PE) ordering (called "feathering") designed to reduce image artifacts is described, and the contributions of RF (B(1)) inhomogeneity, different echo coherence pathways, and magnetization transfer (MT) to FSE signal intensity and contrast are investigated. B(1) inhomogeneity is measured and its effect is shown to be relatively minor for high-field FSE, due to the self-compensating characteristics of the sequence. Thirty-four slice data sets (slice thickness = 2 mm; in-plane resolution = 0.469 mm; acquisition time = 11 min 20 s) from normal volunteers are presented, which allow visualization of brain anatomy in fine detail. This study demonstrates that high-field FSE produces images of the human brain with high spatial resolution, SNR, and tissue contrast, within currently prescribed power deposition guidelines.

Adult↗

PubMed2004

The MR detection of neuronal depolarization during 3-Hz spike-and-wave complexes in generalized epilepsy.

Previously, an analysis of activations observed in a patient with idiopathic generalized epilepsy using electroencephalogram-correlated functional magnetic resonance imaging (MRI) during runs of 3-Hz generalized spike-wave discharge (GSWD) was presented by Salek-Haddadi. Time-locked, bilateral, thalamic blood oxygenation level-dependent increases were reported to be accompanied by widespread, symmetric, cortical deactivation with a frontal maximum. In light of recent investigations into MRI detection of the magnetic field perturbations caused by neuronal current loops during depolarization, we revisited the analysis of the data of Salek-Haddadi as a preliminary search for a neuroelectric signal. We modeled the MRI response as the sum of a fast signal and a slower signal and demonstrated significant MRI activity at a time scale of the order of 30 ms associated with GSWDs. Further work is necessary before firm conclusions may be drawn about the nature of this signal.

Cerebral Cortex↗

PubMed2004

Assessment of health state utilities and quality of life in patients with malignant esophageal Dysphagia.

OBJECTIVES: Palliation of terminal conditions such as malignant dysphagia must take into account individual preferences for aggressive or nonaggressive care, with a focus on quality of life. Despite this, there are very few data on patients' preferences for palliative therapy. This study is designed to quantitatively determine individual preferences for palliation of malignant dysphagia using health state utilities (HSU). METHODS: HSU were measured using three methods: time trade-off (TTO), visual analog scale (VAS), and the EQ-5D. Patients with esophageal cancer were asked to rate their own state of health and of three standardized scenarios of local, regional, and metastatic disease. RESULTS: Fifty patients with esophageal cancer were enrolled. Using the TTO method, the utilities of their own health state were 0.80 (95% CI 0.59-0.99) for localized, 0.54 (0.37-0.70) for regional, and 0.52 (0.32-0.71) for metastatic cancer showing no significant difference in mean utility scores for the three staging groups. VAS and EQ5D gave statistically similar values to TTO. Patients consistently rated their own utility better than the utility of standardized scenarios with similar stage and prognosis. Independent of their staging, patients with high dysphagia scores rated their utility worse than patients with low dysphagia scores. CONCLUSIONS: These results confirm the perceived poor state of health of patients with esophageal cancer and are substantially lower than previous estimates in operated patients. Cost-effectiveness models must take into account significant differences between patients' assessment of their own state of health, and that of a "societal" perspective of others with a similar disease. All three methods provided similar estimates. Given the ease of use of VAS and EQ-5D, these methods may be preferable to TTO.

Activities of Daily Living↗

PubMed2003

Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE: A phase II trial was performed to evaluate the efficacy, tolerance, and pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB; Pierre Fabre Médicament, Boulogne, France) was given as first-line chemotherapy for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS: Sixty-four patients were entered to receive oral NVB on a weekly basis for a total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at 60 mg/m(2) weekly for the first three administrations and was increased to 80 mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Patients with objective response or stable disease continued treatment up to a total of 12 weeks or more. RESULTS: Fifty-eight evaluable patients were included in our study. Four patients (6.9%) had complete responses, and 14 (24.1%) had partial responses, for an overall response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was 17.4 weeks. Median overall survival is not yet reached. There were no treatment-related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the patients, and 1.8% of administrations and associated clinical serious events in 4 patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6% of the patients, respectively. Only one patient developed grade 3 neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms revealed no significant alteration between baseline and weeks 8 and 16 in global quality of life. CONCLUSION: Oral NVB at this schedule is an effective and well-tolerated agent in the treatment of ABC and offers a promising alternative to the intravenous route. Combination studies are ongoing.

Administration, Oral↗

PubMed2003

Brain changes after learning to read and play music.

Musically naive participants were scanned before and after a period of 15 weeks during which they were taught to read music and play the keyboard. When participants played melodies from musical notation after training, activation was seen in a cluster of voxels within the bilateral superior parietal cortex. A subset of these voxels were activated in a second experiment in which musical notation was present, but irrelevant for task performance. These activations suggest that music reading involves the automatic sensorimotor translation of a spatial code (written music) into a series of motor responses (keypresses).

Adult↗

PubMed2003

Techniques for imaging neuroscience.

In the last 20 years, a number of non-invasive spatial mapping techniques have been demonstrated to provide powerful insights into the operation of the brain during task performance. These are, in order of their emergence as robust technologies: positron emission tomography, source localization with EEG and MEG, and functional magnetic resonance imaging. The imaging neuroscience study areas represented in this volume use the first or last of these - PET and fMRI. The physical principles underlying both of these techniques are outlined, and the important assumptions and limitations are made explicit. The range of applications for each is briefly indicated.

Brain↗