The impact of variations in subject geometry, respiration and coil repositioning on the specific absorption rate in parallel transmit abdominal imaging at 7 T.

Parallel transmit MRI at 7 T has increasingly been adopted in research projects and provides increased signal-to-noise ratios and novel contrasts. However, the interactions of fields in the body need to be carefully considered to ensure safe scanning. Recent advances in physically flexible body coils have allowed for high-field abdominal imaging, but the effects of increased variability on energy deposition need further exploration. The aim of this study was to assess the impact of subject geometry, respiration phase and coil positioning on the specific absorption rate (SAR). Ten healthy subjects (body mass index [BMI] = 25 ± 5 kg m-2 ) were scanned (at 3 T) during exhale breath-hold and images used to generate body models. Seven of these subjects were also scanned during inhale. Simplifications of the coil and body models were first explored, and then finite-difference time-domain simulations were run with a typical eight-channel parallel transmit coil positioned over the abdomen. Simulations were used to generate 10 g averaged SAR (SAR10g ) maps across 100,000 phase settings, and the worst-case scenario 10 g averaged SAR (wocSAR10g ) was identified using trigonometric maximisation. The average maximum SAR10g across the 10 subjects with 1 W input power per channel was 1.77 W kg-1 . Hotspots were always close to the body surface near the muscle wall boundary. The wocSAR10g across the 10 subjects ranged from 2.3 to 3.2 W kg-1 and was inversely correlated to fat volume percentage (R = 8) and BMI (R = 0.6). The coefficient of variation values in SAR10g due to variations in subject geometry, respiration phase and realistic coil repositioning were 12%, 4% and 12%, respectively. This study found that the variability due to realistic coil repositioning was similar to the variability due to differing healthy subject geometries for abdominal imaging. This is important as it suggests that population-based modelling is likely to be more useful than individual modelling in setting safe thresholds for abdominal imaging.

Predicting cytopenias, progression, and survival in patients with clonal cytopenia of undetermined significance: a prospective cohort study.

BACKGROUND: Somatic mutations are frequently reported in individuals with cytopenia but without a confirmed haematological diagnosis (clonal cytopenia of undetermined significance; CCUS). These patients have an increased risk of progression to a myeloid malignancy and worse overall survival than those with no such mutations. To date, studies have been limited by retrospective analysis or small patient numbers. We aimed to establish the natural history of CCUS by prospectively investigating outcome in a large, well defined patient cohort. METHODS: This prospective cohort study was conducted at the Haematological Malignancy Diagnostic Service, a diagnostic laboratory in Leeds, UK. Patients aged at least 18 years who were referred for investigation of cytopenia were eligible for inclusion; those with a history of myeloid malignancy were not eligible. Targeted sequencing was conducted alongside routine clinical testing. Baseline mutation analysis was then correlated with the main study outcomes: longitudinal blood counts, disease progression to a myeloid malignancy, and overall survival with a median follow-up of 4·54 years (IQR 4·03-5·04). Data were collected manually from hospital records or extracted from laboratory or clinical outcome databases. FINDINGS: Bone marrow samples from 2348 patients were received at the Haematological Malignancy Diagnostic Service between July 1, 2014, and July 31, 2016. Of these, 2083 patients (median age 72 years [IQR 63-80, range 18-99]; 854 [41·0%] female and 1229 [59·0%] male) met the inclusion criteria and had samples of sufficient quality for further analysis. 598 (28·7%) patients received a diagnosis on the basis of their biopsy sample, whereas 1485 (71·3%) samples were classified as non-diagnostic; of these, CCUS was confirmed in 400 (26·9%) patients (256 [64·0%] male and 144 [36·0%] female). TET2, SRSF2, and DNMT3A were the most frequently mutated genes in patients with CCUS, with 320 (80%) of 400 patients harbouring a mutation in at least one of these genes. Age (p<0·0001), sex (p=0·0027), and mutations in ASXL1 (p=0·0009), BCOR (p=0·0056), and TP53 (p=0·0055) correlated with a worse overall survival; however, the number of mutations was the strongest predictor for progression to a myeloid malignancy (two mutations, p=0·0024; three or more mutations, p=0·0004). Extended sequencing of samples from a subgroup of patients with sequential samples and no mutations in the initial myeloid gene panel showed recurrent mutations in both DDX41 and UBA1, suggesting that these genes should be included in clinical test panels. INTERPRETATION: Mutation analysis is advised in patients who have undergone bone marrow examination and have an otherwise-unexplained cytopenia. High-risk genetic mutations and increased numbers of mutations are predictive of both survival and progression within 5 years of presentation, warranting clinical surveillance and, when necessary, intervention. FUNDING: MDS Foundation.

Naturalistic Hyperscanning with Wearable Magnetoencephalography.

The evolution of human cognitive function is reliant on complex social interactions which form the behavioural foundation of who we are. These social capacities are subject to dramatic change in disease and injury; yet their supporting neural substrates remain poorly understood. Hyperscanning employs functional neuroimaging to simultaneously assess brain activity in two individuals and offers the best means to understand the neural basis of social interaction. However, present technologies are limited, either by poor performance (low spatial/temporal precision) or an unnatural scanning environment (claustrophobic scanners, with interactions via video). Here, we describe hyperscanning using wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs). We demonstrate our approach by simultaneously measuring brain activity in two subjects undertaking two separate tasks-an interactive touching task and a ball game. Despite large and unpredictable subject motion, sensorimotor brain activity was delineated clearly, and the correlation of the envelope of neuronal oscillations between the two subjects was demonstrated. Our results show that unlike existing modalities, OPM-MEG combines high-fidelity data acquisition and a naturalistic setting and thus presents significant potential to investigate neural correlates of social interaction.

Enabling ambulatory movement in wearable magnetoencephalography with matrix coil active magnetic shielding.

The ability to collect high-quality neuroimaging data during ambulatory participant movement would enable a wealth of neuroscientific paradigms. Wearable magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has the potential to allow participant movement during a scan. However, the strict zero magnetic field requirement of OPMs means that systems must be operated inside a magnetically shielded room (MSR) and also require active shielding using electromagnetic coils to cancel residual fields and field changes (due to external sources and sensor movements) that would otherwise prevent accurate neuronal source reconstructions. Existing active shielding systems only compensate fields over small, fixed regions and do not allow ambulatory movement. Here we describe the matrix coil, a new type of active shielding system for OPM-MEG which is formed from 48 square unit coils arranged on two planes which can compensate magnetic fields in regions that can be flexibly placed between the planes. Through the integration of optical tracking with OPM data acquisition, field changes induced by participant movement are cancelled with low latency (25 ms). High-quality MEG source data were collected despite the presence of large (65 cm translations and 270° rotations) ambulatory participant movements.

A lightweight magnetically shielded room with active shielding.

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40-60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a 'window coil' active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.

Molecular subclusters of follicular lymphoma: a report from the United Kingdom's Haematological Malignancy Research Network.

Follicular lymphoma (FL) is morphologically and clinically diverse, with mutations in epigenetic regulators alongside t(14;18) identified as disease-initiating events. Identification of additional mutational entities confirms this cancer's heterogeneity, but whether mutational data can be resolved into mechanistically distinct subsets remains an open question. Targeted sequencing was applied to an unselected population-based FL cohort (n = 548) with full clinical follow-up (n = 538), which included 96 diffuse large B-cell lymphoma (DLBCL) transformations. We investigated whether molecular subclusters of FL can be identified and whether mutational data provide predictive information relating to transformation. DNA extracted from FL samples was sequenced with a 293-gene panel representing genes frequently mutated in DLBCL and FL. Three clusters were resolved using mutational data alone, independent of translocation status: FL_aSHM, with high burden of aberrant somatic hypermutation (aSHM) targets; FL_STAT6, with high STAT6 & CREBBP mutation and low aSHM; and FL_Com, with the absence of features of other subtypes and enriched KMT2D mutation. Analysis of mutation signatures demonstrated differential enrichment of predicted mutation signatures between subgroups and a dominant preference in the FL_aSHM subgroup for G(C>T)T and G(C>T)C transitions consistent with previously defined aSHM-like patterns. Of transformed cases with paired samples, 17 of 26 had evidence of branching evolution. Poorer overall survival (OS) in the aSHM group (P = .04) was associated with older age; however, overall tumor genetics provided limited information to predict individual patient risk. Our approach identifies 3 molecular subclusters of FL linked to differences in underlying mechanistic pathways. These clusters, which may be further resolved by the inclusion of translocation status and wider mutation profiles, have implications for understanding pathogenesis as well as improving treatment strategies in the future.

Comparative analysis of gene expression platforms for cell-of-origin classification of diffuse large B-cell lymphoma shows high concordance.

Cell-of-origin subclassification of diffuse large B cell lymphoma (DLBCL) into activated B cell-like (ABC), germinal centre B cell-like (GCB) and unclassified (UNC) or type III by gene expression profiling is recommended in the latest update of the World Health Organization's classification of lymphoid neoplasms. There is, however, no accepted gold standard method or dataset for this classification. Here, we compare classification results using gene expression data for 68 formalin-fixed paraffin-embedded DLBCL samples measured on four different gene expression platforms (Illumina wG-DASLTM arrays, Affymetrix PrimeView arrays, Illumina TrueSeq RNA sequencing and the HTG EdgeSeq DLBCL Cell of Origin Assay EU using an established platform agnostic classification algorithm (DAC) and the classifier native to the HTG platform, which is CE marked for in vitro diagnostic use (CE-IVD). Classification methods and platforms show a high level of concordance, with agreement in at least 80% of cases and rising to much higher levels for classifications of high confidence. Our results demonstrate that cell-of-origin classification by gene expression profiling on different platforms is robust, and that the use of the confidence value alongside the classification result is important in clinical applications.

Qualitative and quantitative assessment of magnetic vestibular stimulation in humans.

The sensation of phantom motion or exhibition of bodily sway is often reported in the proximity of an MR scanner. It is proposed that the magnetic field stimulates the vestibular system. There are a number of possible mechanisms responsible, and the relative contributions of susceptibility on the otolithic receptors and the Lorentz force on the cupulae have not yet been explored. This exploratory study aims to investigate the impact of being in the proximity of a 7.0 T MR scanner.The modified clinical test of sensory interaction on balance (mCTSIB) was used to qualitatively ascertain whether or not healthy control subjects who passed the mCTSIB in normal conditions 1) experienced subjective sensations of dizziness, vertigo or of leaning or shifting in gravity when in the magnetic field and 2) exhibited visibly increased bodily sway whilst in the magnetic field compared to outside the magnetic field. Condition IV of the mCTSIB was video recorded outside and inside the magnetic field, providing a semi-quantitative measure of sway.For condition IV of the mCTSIB (visual and proprioceptive cues compromised), all seven locations/orientations around the scanner yielded significantly more sway than at baseline (p < 0.01 FDR). A Student's t-test comparing the RMS velocity of a motion marker on the upper arm during mCTSIB condition IV showed a significant increase in the amount of motion exhibited in the field (T = 2.59; d.f. = 9; p = 0.029) compared to outside the field.This initial study using qualitative measures of sway demonstrates that there is evidence for MR-naïve individuals exhibiting greater sway while performing the mCTSIB in the magnetic field compared to outside the field. Directional polarity of sway was not significant. Future studies of vestibular stimulation by magnetic fields would benefit from the development of a sensitive, objective measure of balance function, which can be performed inside a magnetic field.

Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants.

OBJECTIVE: The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo data is available on undisturbed gastrointestinal motility to improve relevance of predictive dissolution models and in silico tools such as physiologically-based pharmacokinetic models. Recent advances in magnetic resonance imaging methods could provide novel data and insights that can be used as a reference to validate and, if necessary, optimize these models. The conventional method for measuring gastrointestinal motility is via a manometric technique involving intubation. Nevertheless, it is feasible to measure gastrointestinal motility with magnetic resonance imaging. The aim of this study was is to develop and validate a magnetic resonance imaging method using the most recent semi-automated analysis method against concomitant perfused manometry method. MATERIAL AND METHODS: Eighteen healthy fasted participants were recruited for this study. The participants were intubated with a water-perfused manometry catheter. Subsequently, stomach motility was assessed by cine-MRI acquired at intervals, of 3.5min sets, at coronal oblique planes through the abdomen and by simultaneous water perfused manometry, before and after administration of a standard bioavailability / bioequivalence 8 ounces (~240mL) drink of water. The magnetic resonance imaging motility images were analysed using Spatio-Temporal Motility analysis STMM techniques. The area under the curve of the gastric motility contractions was calculated for each set and compared between techniques. The study visit was then repeated one week later. RESULTS: Data from 15 participants was analysed. There was a good correlation between the MRI antral motility plots area under the curve and corresponding perfused manometry motility area under the curve (r = 0.860) during both antral contractions and quiescence. CONCLUSION: Non-invasive dynamic magnetic resonance imaging of gastric antral motility coupled with recently developed, semi-automated magnetic resonance imaging data processing techniques correlated well with simultaneous, 'gold standard' water perfused manometry. This will be particularly helpful for research purposes related to oral absorption where the absorption of a drug is highly depending on the underlying gastrointestinal processes such as gastric emptying, gastrointestinal motility and availability of residual fluid volumes. CLINICAL TRIAL: This trial was registered at ClinicalTrials.gov as NCT03191045.

Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report.

Based on the profile of genetic alterations occurring in tumor samples from selected diffuse large B-cell lymphoma (DLBCL) patients, 2 recent whole-exome sequencing studies proposed partially overlapping classification systems. Using clustering techniques applied to targeted sequencing data derived from a large unselected population-based patient cohort with full clinical follow-up (n = 928), we investigated whether molecular subtypes can be robustly identified using methods potentially applicable in routine clinical practice. DNA extracted from DLBCL tumors diagnosed in patients residing in a catchment population of ∼4 million (14 centers) were sequenced with a targeted 293-gene hematological-malignancy panel. Bernoulli mixture-model clustering was applied and the resulting subtypes analyzed in relation to their clinical characteristics and outcomes. Five molecular subtypes were resolved, termed MYD88, BCL2, SOCS1/SGK1, TET2/SGK1, and NOTCH2, along with an unclassified group. The subtypes characterized by genetic alterations of BCL2, NOTCH2, and MYD88 recapitulated recent studies showing good, intermediate, and poor prognosis, respectively. The SOCS1/SGK1 subtype showed biological overlap with primary mediastinal B-cell lymphoma and conferred excellent prognosis. Although not identified as a distinct cluster, NOTCH1 mutation was associated with poor prognosis. The impact of TP53 mutation varied with genomic subtypes, conferring no effect in the NOTCH2 subtype and poor prognosis in the MYD88 subtype. Our findings confirm the existence of molecular subtypes of DLBCL, providing evidence that genomic tests have prognostic significance in non-selected DLBCL patients. The identification of both good and poor risk subtypes in patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) clearly show the clinical value of the approach, confirming the need for a consensus classification.

Traumatic right diaphragmatic rupture with hepatothorax in Ghana: two rare cases.

A rare case series of traumatic right diaphragmatic rupture with hepatothorax in Ghana is reported. The first case involved a middle-aged man who sustained a penetrating chest injury following an unprovoked attack by a wild bull. The second case was a young woman who sustained a blunt chest injury after being knocked down by a moving vehicle whiles crossing the road. Both presented with ruptured right diaphgramatic rupture and had to undergo repair through thoracotomy after stabilization and the two had been well one year after surgery without any complications or sequelae.

Catamenial pneumothorax in Ghana: case report and literature review.

Catamenial pneumothorax is a rare condition that is often misdiagnosed. It is defined as spontaneous pneumothorax occurring within 72 hours before or after onset of menstruation. Etiology is unknown but could be linked to endometriosis. Pleural ablation via thoracoscopy and hormonal therapy are mainstay treatment options to avoid recurrence. We present a case of a young adult female who experienced gradual painless abdominal distention that resolved spontaneously after each menses twelve years post menarche. She was first seen at a peripheral facility where laparotomy undertaken was negative for suspected ectopic pregnancy. However, a bleeding omental mass was noticed and a biopsy taken. Histopathology reported it as an endometriotic tissue. The patient subsequently had recurrent cyclical chest pains and breathlessness leading to the diagnosis of catamenial pneumothorax. She had chemical pleurodesis done with sterile talc after chest tube drainage and has been well over two years now.

Carbon quantum dots with tracer-like breakthrough ability for reservoir characterization.

Predictions have shown that our demand for oil and gas will continue to grow in the next decade, and future supply will become more reliant on tertiary recovery and from nonconventional resources. However, current reservoir characterization methodologies, such as well logs, cross-well electromagnetic imaging and seismic methods, have their individual limitations on detection range and resolution. Here we propose a pioneering way to use carbon quantum dots (CQDs) as nanoparticle tracers, which can be transported through a reservoir functioning as conventional tracers, while acting as sensors to obtain useful information. These hydrothermally produced CQDs from Xylose possess excellent stability in high ionic strength solutions, durable absorbance and fluorescence ability due to multi high-polarity functional group on their surfaces. Consistency between our on-line ultraviolet-visible (UV-Vis) spectroscopy and off-line Confocal laser scanning microscopy (CLSM) measurements confirms that CQDs have the tracer-like migration capability in glass beads-packed columns and sandstone cores, regardless of particle concentration and ionic strength. However, their migration ability is undermined in the column packed with crushed calcite grains with positive charge. We also demonstrate that quantitative oil saturation detection in unknown sandstone core samples can be achieved by such CQDs based on its breakthrough properties influenced by the presence of oil phase.

The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis.

The diagnosis of chronic myelomonocytic leukemia (CMML) remains centered on morphology, meaning that the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis; however, they have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel with current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (N = 283). Results were correlated with the morphological diagnosis and objective outcome measures, including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79% of patients, being invariably identified in those with a confirmed diagnosis (99%) but also in 57% of patients with nondiagnostic bone marrow features. The OS in nondiagnostic mutated patients was indistinguishable from those with CMML (P = .118) and significantly worse than in unmutated patients (P = .0002). On multivariate analysis, age, ASXL1, CBL, DNMT3A, NRAS, and RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive decrease in hemoglobin/platelet levels and increasing monocyte counts compared with mutation-negative patients. Of note, the immunophenotypic features of nondiagnostic mutated patients were comparable to CMML patients, and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis, irrespective of diagnosis. In those without a World Health Organization-defined diagnosis, the mutation spectrum, immunophenotypic features, and OS are indistinguishable from CMML patients, and these patients should be managed as such.

Imaging human cortical responses to intraneural microstimulation using magnetoencephalography.

The sensation of touch in the glabrous skin of the human hand is conveyed by thousands of fast-conducting mechanoreceptive afferents, which can be categorised into four distinct types. The spiking properties of these afferents in the periphery in response to varied tactile stimuli are well-characterised, but relatively little is known about the spatiotemporal properties of the neural representations of these different receptor types in the human cortex. Here, we use the novel methodological combination of single-unit intraneural microstimulation (INMS) with magnetoencephalography (MEG) to localise cortical representations of individual touch afferents in humans, by measuring the extracranial magnetic fields from neural currents. We found that by assessing the modulation of the beta (13-30 Hz) rhythm during single-unit INMS, significant changes in oscillatory amplitude occur in the contralateral primary somatosensory cortex within and across a group of fast adapting type I mechanoreceptive afferents, which corresponded well to the induced response from matched vibrotactile stimulation. Combining the spatiotemporal specificity of MEG with the selective single-unit stimulation of INMS enables the interrogation of the central representations of different aspects of tactile afferent signalling within the human cortices. The fundamental finding that single-unit INMS ERD responses are robust and consistent with natural somatosensory stimuli will permit us to more dynamically probe the central nervous system responses in humans, to address questions about the processing of touch from the different classes of mechanoreceptive afferents and the effects of varying the stimulus frequency and patterning.

An intra-neural microstimulation system for ultra-high field magnetic resonance imaging and magnetoencephalography.

BACKGROUND: Intra-neural microstimulation (INMS) is a technique that allows the precise delivery of low-current electrical pulses into human peripheral nerves. Single unit INMS can be used to stimulate individual afferent nerve fibres during microneurography. Combining this with neuroimaging allows the unique monitoring of central nervous system activation in response to unitary, controlled tactile input, with functional magnetic resonance imaging (fMRI) providing exquisite spatial localisation of brain activity and magnetoencephalography (MEG) high temporal resolution. NEW METHOD: INMS systems suitable for use within electrophysiology laboratories have been available for many years. We describe an INMS system specifically designed to provide compatibility with both ultra-high field (7T) fMRI and MEG. Numerous technical and safety issues are addressed. The system is fully analogue, allowing for arbitrary frequency and amplitude INMS stimulation. RESULTS: Unitary recordings obtained within both the MRI and MEG screened-room environments are comparable with those obtained in 'clean' electrophysiology recording environments. Single unit INMS (current <7µA, 200µs pulses) of individual mechanoreceptive afferents produces appropriate and robust responses during fMRI and MEG. COMPARISON WITH EXISTING METHOD(S): This custom-built MRI- and MEG-compatible stimulator overcomes issues with existing INMS approaches; it allows well-controlled switching between recording and stimulus mode, prevents electrical shocks because of long cable lengths, permits unlimited patterns of stimulation, and provides a system with improved work-flow and participant comfort. CONCLUSIONS: We demonstrate that the requirements for an INMS-integrated system, which can be used with both fMRI and MEG imaging systems, have been fully met.

A new generation of magnetoencephalography: Room temperature measurements using optically-pumped magnetometers.

Advances in the field of quantum sensing mean that magnetic field sensors, operating at room temperature, are now able to achieve sensitivity similar to that of cryogenically cooled devices (SQUIDs). This means that room temperature magnetoencephalography (MEG), with a greatly increased flexibility of sensor placement can now be considered. Further, these new sensors can be placed directly on the scalp surface giving, theoretically, a large increase in the magnitude of the measured signal. Here, we present recordings made using a single optically-pumped magnetometer (OPM) in combination with a 3D-printed head-cast designed to accurately locate and orient the sensor relative to brain anatomy. Since our OPM is configured as a magnetometer it is highly sensitive to environmental interference. However, we show that this problem can be ameliorated via the use of simultaneous reference sensor recordings. Using median nerve stimulation, we show that the OPM can detect both evoked (phase-locked) and induced (non-phase-locked oscillatory) changes when placed over sensory cortex, with signals ~4 times larger than equivalent SQUID measurements. Using source modelling, we show that our system allows localisation of the evoked response to somatosensory cortex. Further, source-space modelling shows that, with 13 sequential OPM measurements, source-space signal-to-noise ratio (SNR) is comparable to that from a 271-channel SQUID system. Our results highlight the opportunity presented by OPMs to generate uncooled, potentially low-cost, high SNR MEG systems.

Synthetic Fractal Modelling of Heterogeneous and Anisotropic Reservoirs for Use in Simulation Studies: Implications on Their Hydrocarbon Recovery Prediction.

Optimising production from heterogeneous and anisotropic reservoirs challenges the modern hydrocarbon industry because such reservoirs exhibit extreme inter-well variability making them very hard to model. Reasonable reservoir models can be obtained using modern geostatistical techniques, but all of them rely on significant variability in the reservoir only occurring at a scale at or larger than the inter-well spacing. In this paper we take a different, generic approach. We have developed a method for constructing realistic synthetic heterogeneous and anisotropic reservoirs which can be made to represent the reservoir under test. The main physical properties of these synthetic reservoirs are distributed fractally. The models are fully controlled and reproducible and can be extended to model multiple facies reservoir types. This paper shows how the models can be constructed and how they have been tested. Reservoir simulation results of a number of generated 3-D heterogeneous and anisotropic models show that heterogeneity, in terms of only the geometric distribution of reservoir properties, has a little effect on oil production from high and moderate quality reservoirs. However, if the effect of heterogeneity on capillary pressure is taken into account, the effect becomes striking, where varying the heterogeneity of reservoirs properties can lead to a 70 % change in the predicted oil production rate and a significant early shift of water breakthrough time. Hence, it is the heterogeneity consequences that are really substantial if not taken into account. These are very significant uncertainties for a hydrocarbon company if the heterogeneity of their reservoir is not well defined.

Diagnostic accuracy of the Kampala Trauma Score using estimated Abbreviated Injury Scale scores and physician opinion.

BACKGROUND: The Kampala Trauma Score (KTS) has been proposed as a triage tool for use in low- and middle-income countries (LMICs). This study aimed to examine the diagnostic accuracy of KTS in predicting emergency department outcomes using timely injury estimation with Abbreviated Injury Scale (AIS) score and physician opinion to calculate KTS scores. METHODS: This was a diagnostic accuracy study of KTS among injured patients presenting to Komfo Anokye Teaching Hospital A&E, Ghana. South African Triage Scale (SATS); KTS component variables, including AIS scores and physician opinion for serious injury quantification; and ED disposition were collected. Agreement between estimated AIS score and physician opinion were analyzed with normal, linear weighted, and maximum kappa. Receiver operating characteristic (ROC) analysis of KTS-AIS and KTS-physician opinion was performed to evaluate each measure's ability to predict A&E mortality and need for hospital admission to the ward or theatre. RESULTS: A total of 1053 patients were sampled. There was moderate agreement between AIS criteria and physician opinion by normal (κ=0.41), weighted (κlin=0.47), and maximum (κmax=0.53) kappa. A&E mortality ROC area for KTS-AIS was 0.93, KTS-physician opinion 0.89, and SATS 0.88 with overlapping 95% confidence intervals (95%CI). Hospital admission ROC area for KTS-AIS was 0.73, KTS-physician opinion 0.79, and SATS 0.71 with statistical similarity. When evaluating only patients with serious injuries, KTS-AIS (ROC 0.88) and KTS-physician opinion (ROC 0.88) performed similarly to SATS (ROC 0.78) in predicting A&E mortality. The ROC area for KTS-AIS (ROC 0.71; 95%CI 0.66-0.75) and KTS-physician opinion (ROC 0.74; 95%CI 0.69-0.79) was significantly greater than SATS (ROC 0.57; 0.53-0.60) with regard to need for admission. CONCLUSIONS: KTS predicted mortality and need for admission from the ED well when early estimation of the number of serious injuries was used, regardless of method (i.e. AIS criteria or physician opinion). This study provides evidence for KTS to be used as a practical and valid triage tool to predict patient prognosis, ED outcomes and inform referral decision-making from first- or second-level hospitals in LMICs.

Mapping quantal touch using 7 Tesla functional magnetic resonance imaging and single-unit intraneural microstimulation.

Using ultra-high field 7 Tesla (7T) functional magnetic resonance imaging (fMRI), we map the cortical and perceptual responses elicited by intraneural microstimulation (INMS) of single mechanoreceptive afferent units in the median nerve, in humans. Activations are compared to those produced by applying vibrotactile stimulation to the unit's receptive field, and unit-type perceptual reports are analyzed. We show that INMS and vibrotactile stimulation engage overlapping areas within the topographically appropriate digit representation in the primary somatosensory cortex. Additional brain regions in bilateral secondary somatosensory cortex, premotor cortex, primary motor cortex, insula and posterior parietal cortex, as well as in contralateral prefrontal cortex are also shown to be activated in response to INMS. The combination of INMS and 7T fMRI opens up an unprecedented opportunity to bridge the gap between first-order mechanoreceptive afferent input codes and their spatial, dynamic and perceptual representations in human cortex.