Evaluation of atlas-based segmentation of hippocampi in healthy humans

Introduction and aim: Region of interest (ROI)-based functional magnetic resonance imaging (fMRI) data analysis relies on extracting signals from a specific area which is presumed to be involved in the brain activity being studied. The hippocampus is of interest in many functional connectivity studies for example in epilepsy as it plays an important role in epileptogenesis. In this context, ROI may be defined using different techniques. Our study aims at evaluating the spatial correspondence of hippocampal ROIs obtained using three brain atlases with hippocampal ROI obtained using an automatic segmentation algorithm dedicated to the hippocampus. Material and methods: High-resolution volumetric T1-weighted MR images of 18 healthy volunteers (five females) were acquired on a 3T scanner. Individual ROIs for both hippocampi of each subject were segmented from the MR images using an automatic hippocampus and amygdala segmentation software called SACHA providing the gold standard ROI for comparison with the atlas-derived results. For each subject, hippocampal ROIs were also obtained using three brain atlases: PickAtlas available as a commonly used software toolbox; automated anatomical labeling (AAL) atlas included as a subset of ROI into PickAtlas toolbox and a frequency-based brain atlas by Hammers et al. The levels of agreement between the SACHA results and those obtained using the atlases were assessed based on quantitative indices measuring volume differences and spatial overlap. The comparison was performed in standard Montreal Neurological Institute space, the registration being obtained with SPM5 (http://www.fil.ion.ucl.ac.uk/spm/). Results: The mean volumetric error across all subjects was 73% for hippocampal ROIs derived from AAL atlas; 20% in case of ROIs derived from the Hammers atlas and 107% for ROIs derived from PickAtlas. The mean false-positive and false-negative classification rates were 60% and 10% respectively for the AAL atlas; 16% and 32% for the Hammers atlas and 6% and 72% for the PickAtlas. Conclusion: Though atlas-based ROI definition may be convenient, the resulting ROIs may be poor representations of the hippocampus in some studies critical to under- or oversampling. Performance of the AAL atlas was inferior to that of the Hammers atlas. Hippocampal ROIs derived from PickAtlas are highly significantly smaller, and this results in the worst performance out of three atlases. It is advisable that the defined ROIs should be verified with knowledge of neuroanatomy before using it for further data analysis

The spatio-temporal mapping of epileptic networks: Combination of EEG–fMRI and EEG source imaging

Simultaneous EEG–fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG–fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG–fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG–fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks

Assortative mixing as a source of bias in epidemiological studies of sexually transmitted infections: the case of smoking and human papillomavirus

For studies examining risk factors of sexually transmitted infections (STIs), confounding can stem from characteristics of partners of study subjects, and persist after adjustment for the subjects’ individual-level characteristics. Two conditions that can result in confounding by the subjects’ partners are: (C1) partner choice is assortative by the risk factor examined and, (C2) sexual activity is associated with the risk factor. The objective of this paper is to illustrate the potential impact of the assortativity bias in studies examining STI risk factors, using smoking and human papillomavirus (HPV) as an example. We developed an HPV transmission-dynamic mathematical model in which we nested a cross-sectional study assessing the smoking–HPV association. In our base case, we assumed (1) no effect of smoking on HPV, and (2) conditions C1–C2 hold for smoking (based on empirical data). The assortativity bias caused an overestimation of the odds ratio (OR) in the simulated study after perfect adjustment for the subjects’ individual-level characteristics (adjusted OR 1·51 instead of 1·00). The bias was amplified by a lower basic reproductive number (R(0)), greater mixing assortativity and stronger association of smoking with sexual activity. Adjustment for characteristics of partners is needed to mitigate assortativity bias

EEG correlated functional MRI and postoperative outcome in focal epilepsy

Background: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset. Frequently, identification of the irritative and seizure onset zones requires invasive EEG. EEG correlated functional MRI (EEG-fMRI) is a novel imaging technique which may provide localising information with regard to these regions. In patients with focal epilepsy, interictal epileptiform discharge (IED) correlated blood oxygen dependent level (BOLD) signal changes were observed in approximately 50% of patients in whom IEDs are recorded. In 70%, these are concordant with expected seizure onset defined by non-invasive electroclinical information. Assessment of clinical validity requires post-surgical outcome studies which have, to date, been limited to case reports of correlation with intracranial EEG. The value of EEG-fMRI was assessed in patients with focal epilepsy who subsequently underwent epilepsy surgery, and IED correlated fMRI signal changes were related to the resection area and clinical outcome. Methods: Simultaneous EEG-fMRI was recorded in 76 patients undergoing presurgical evaluation and the locations of IED correlated preoperative BOLD signal change were compared with the resected area and postoperative outcome. Results: 21 patients had activations with epileptic activity on EEG-fMRI and 10 underwent surgical resection. Seven of 10 patients were seizure free following surgery and the area of maximal BOLD signal change was concordant with resection in six of seven patients. In the remaining three patients, with reduced seizure frequency post-surgically, areas of significant IED correlated BOLD signal change lay outside the resection. 42 of 55 patients who had no IED related activation underwent resection. Conclusion: These results show the potential value of EEG-fMRI in presurgical evaluation

Topological transitions in carbon nanotube networks via nanoscale confinement

Efforts aimed at large-scale integration of nanoelectronic devices that exploit the superior electronic and mechanical properties of single-walled carbon nanotubes (SWCNTs) remain limited by the difficulties associated with manipulation and packaging of individual SWNTs. Alternative approaches based on ultra-thin carbon nanotube networks (CNNs) have enjoyed success of late with the realization of several scalable device applications. However, precise control over the network electronic transport is challenging due to i) an often uncontrollable interplay between network coverage and its topology and ii) the inherent electrical heterogeneity of the constituent SWNTs. In this letter, we use template-assisted fluidic assembly of SWCNT networks to explore the effect of geometric confinement on the network topology. Heterogeneous SWCNT networks dip-coated onto sub-micron wide ultra-thin polymer channels exhibit a topology that becomes increasingly aligned with decreasing channel width and thickness. Experimental scale coarse-grained computations of interacting SWCNTs show that the effect is a reflection of an aligned topology that is no longer dependent on the network density, which in turn emerges as a robust knob that can induce semiconductor-to-metallic transitions in the network response. Our study demonstrates the effectiveness of directed assembly on channels with varying degrees of confinement as a simple tool to tailor the conductance of the otherwise heterogeneous network, opening up the possibility of robust large-scale CNN-based devices.Comment: 4 pages, 3 figure

An ensemble-based approach for pumping optimization in an island aquifer considering parameter, observation and climate uncertainty

In coastal zones, a major objective of groundwater management is often to determine sustainable pumping rates which avoid well salinization. Understanding how model and climate uncertainties affect optimal management solutions is essential for providing groundwater managers with information about salinization risk and is facilitated by the use of optimization under uncertainty (OUU) methods. However, guidelines are missing for the widespread implementation of OUU in real-world coastal aquifers and for the incorporation of climate uncertainty into OUU approaches. An ensemble-based OUU approach was developed considering parameter, observation and climate uncertainty and was implemented in a real-world island aquifer in the Magdalen Islands (Quebec, Canada). A sharp-interface seawater intrusion model was developed using MODFLOW-SWI2 and a prior parameter ensemble was generated containing multiple equally plausible realizations. Ensemble-based history matching was conducted using an iterative ensemble smoother which yielded a posterior parameter ensemble conveying both parameter and observation uncertainty. Sea level and recharge ensembles were generated for the year 2050 and were then used to generate a predictive parameter ensemble conveying parameter, observation and climate uncertainty. Multi-objective OUU was then conducted, aiming to both maximize pumping rates and minimize the probability of well salinization. As a result, the optimal trade-off between pumping and the probability of salinization was quantified considering parameter, historical observation and future climate uncertainty simultaneously. The multi-objective, ensemble-based OUU led to optimal pumping rates that were very different from a previous deterministic OUU and close to the current and projected water demand for risk-averse stances. Incorporating climate uncertainty into the OUU was also critical since it reduced the maximum allowable pumping rates for users with a risk-averse stance. The workflow used tools adapted to very high-dimensional, nonlinear models and optimization problems to facilitate its implementation in a wide range of real-world settings.</p

Stressed backbone and elasticity of random central-force systems

We use a new algorithm to find the stress-carrying backbone of ``generic'' site-diluted triangular lattices of up to 10^6 sites. Generic lattices can be made by randomly displacing the sites of a regular lattice. The percolation threshold is Pc=0.6975 +/- 0.0003, the correlation length exponent \nu =1.16 +/- 0.03 and the fractal dimension of the backbone Db=1.78 +/- 0.02. The number of ``critical bonds'' (if you remove them rigidity is lost) on the backbone scales as L^{x}, with x=0.85 +/- 0.05. The Young's modulus is also calculated.Comment: 5 pages, 5 figures, uses epsfi

How can we improve guideline use? A conceptual framework of implementability

BACKGROUND: Guidelines continue to be underutilized, and a variety of strategies to improve their use have been suboptimal. Modifying guideline features represents an alternative, but untested way to promote their use. The purpose of this study was to identify and define features that facilitate guideline use, and examine whether and how they are included in current guidelines. METHODS: A guideline implementability framework was developed by reviewing the implementation science literature. We then examined whether guidelines included these, or additional implementability elements. Data were extracted from publicly available high quality guidelines reflecting primary and institutional care, reviewed independently by two individuals, who through discussion resolved conflicts, then by the research team. RESULTS: The final implementability framework included 22 elements organized in the domains of adaptability, usability, validity, applicability, communicability, accommodation, implementation, and evaluation. Data were extracted from 20 guidelines on the management of diabetes, hypertension, leg ulcer, and heart failure. Most contained a large volume of graded, narrative evidence, and tables featuring complementary clinical information. Few contained additional features that could improve guideline use. These included alternate versions for different users and purposes, summaries of evidence and recommendations, information to facilitate interaction with and involvement of patients, details of resource implications, and instructions on how to locally promote and monitor guideline use. There were no consistent trends by guideline topic. CONCLUSIONS: Numerous opportunities were identified by which guidelines could be modified to support various types of decision making by different users. New governance structures may be required to accommodate development of guidelines with these features. Further research is needed to validate the proposed framework of guideline implementability, develop methods for preparing this information, and evaluate how inclusion of this information influences guideline use

Granular flow down a rough inclined plane: transition between thin and thick piles

The rheology of granular particles in an inclined plane geometry is studied using molecular dynamics simulations. The flow--no-flow boundary is determined for piles of varying heights over a range of inclination angles $\theta$. Three angles determine the phase diagram: $\theta_{r}$, the angle of repose, is the angle at which a flowing system comes to rest; $\theta_{m}$, the maximum angle of stability, is the inclination required to induce flow in a static system; and $\theta_{max}$ is the maximum angle for which stable, steady state flow is observed. In the stable flow region $\theta_{r}<\theta<\theta_{max}$, three flow regimes can be distinguished that depend on how close $\theta$ is to $\theta_{r}$: i) $\theta>>\theta_{r}$: Bagnold rheology, characterized by a mean particle velocity $v_{x}$ in the direction of flow that scales as $v_{x}\propto h^{3/2}$, for a pile of height $h$, ii) $\theta\gtrsim\theta_{r}$: the slow flow regime, characterized by a linear velocity profile with depth, and iii) $\theta\approx\theta_{r}$: avalanche flow characterized by a slow underlying creep motion combined with occasional free surface events and large energy fluctuations. We also probe the physics of the initiation and cessation of flow. The results are compared to several recent experimental studies on chute flows and suggest that differences between measured velocity profiles in these experiments may simply be a consequence of how far the system is from jamming.Comment: 19 pages, 14 figs, submitted to Physics of Fluid