Non-negative data-driven mapping of structural connections with application to the neonatal brain.

Mapping connections in the neonatal brain can provide insight into the crucial early stages of neurodevelopment that shape brain organisation and lay the foundations for cognition and behaviour. Diffusion MRI and tractography provide unique opportunities for such explorations, through estimation of white matter bundles and brain connectivity. Atlas-based tractography protocols, i.e. a priori defined sets of masks and logical operations in a template space, have been commonly used in the adult brain to drive such explorations. However, rapid growth and maturation of the brain during early development make it challenging to ensure correspondence and validity of such atlas-based tractography approaches in the developing brain. An alternative can be provided by data-driven methods, which do not depend on predefined regions of interest. Here, we develop a novel data-driven framework to extract white matter bundles and their associated grey matter networks from neonatal tractography data, based on non-negative matrix factorisation that is inherently suited to the non-negative nature of structural connectivity data. We also develop a non-negative dual regression framework to map group-level components to individual subjects. Using in-silico simulations, we evaluate the accuracy of our approach in extracting connectivity components and compare with an alternative data-driven method, independent component analysis. We apply non-negative matrix factorisation to whole-brain connectivity obtained from publicly available datasets from the Developing Human Connectome Project, yielding grey matter components and their corresponding white matter bundles. We assess the validity and interpretability of these components against traditional tractography results and grey matter networks obtained from resting-state fMRI in the same subjects. We subsequently use them to generate a parcellation of the neonatal cortex using data from 323 new-born babies and we assess the robustness and reproducibility of this connectivity-driven parcellation.

Optimal Conditions for the Direct RP-HPLC Determination of Underivatized Amino Acids with Online Multiple Detection.

The combined use of a dual-UV detector as well as a fluorimetric and a multielectrode electrochemical detector (equipped with a dual electrode, consisting of a conventional size 3 mm diameter glassy carbon electrode (GCE) and of a pair of 30 µm thick carbon microfibers) is proposed for the detection of the following 15 underivatized amino acids: L-histidine (His), L-cysteine (Cys), creatine (Crn), S-methyl-L-cysteine (Me-Cys), DL-homocysteine (Hcy), L-methionine (Met), beta-(3,4-dihydroxyphenyl)-L-alanine (DOPA), L-tyrosine (Tyr), DL-m-tyrosine (m-Tyr), L-a-methyl-DOPA (Me-DOPA), L-phenylalanine (Phe), DL-alpha-methyltyrosine (Me-Tyr), 5-hydroxy-tryptophan (5-HTP), 3-nitro-L-tyrosine (NO2Tyr), and L-tryptophan (Trp), as well as of 2 dipeptides L-cystathionine (Cysta) and L-carnosine (Car), and of creatinine (Cre). A multilinear solvent (acetonitrile) gradient elution program, determined by a simple optimization algorithm, is required for the efficient reversed-phase separation of the above mixture of 18 solutes within 27 min at a flow rate of 1.0 mL/min and at 25 °C.

Broadband luminescence in defect-engineered electrochemically produced porous Si/ZnO nanostructures.

The fabrication, by an all electrochemical process, of porous Si/ZnO nanostructures with engineered structural defects, leading to strong and broadband deep level emission from ZnO, is presented. Such nanostructures are fabricated by a combination of metal-assisted chemical etching of Si and direct current electrodeposition of ZnO. It makes the whole fabrication process low-cost, compatible with Complementary Metal-Oxide Semiconductor technology, scalable and easily industrialised. The photoluminescence spectra of the porous Si/ZnO nanostructures reveal a correlation between the lineshape, as well as the strength of the emission, with the morphology of the underlying porous Si, that control the induced defects in the ZnO. Appropriate fabrication conditions of the porous Si lead to exceptionally bright Gaussian-type emission that covers almost the entire visible spectrum, indicating that porous Si/ZnO nanostructures could be a cornerstone material towards white-light-emitting devices.

Bayesian Optimisation of Large-Scale Biophysical Networks.

The relationship between structure and function in the human brain is well established, but not yet well characterised. Large-scale biophysical models allow us to investigate this relationship, by leveraging structural information (e.g. derived from diffusion tractography) in order to couple dynamical models of local neuronal activity into networks of interacting regions distributed across the cortex. In practice however, these models are difficult to parametrise, and their simulation is often delicate and computationally expensive. This undermines the experimental aspect of scientific modelling, and stands in the way of comparing different parametrisations, network architectures, or models in general, with confidence. Here, we advocate the use of Bayesian optimisation for assessing the capabilities of biophysical network models, given a set of desired properties (e.g. band-specific functional connectivity); and in turn the use of this assessment as a principled basis for incremental modelling and model comparison. We adapt an optimisation method designed to cope with costly, high-dimensional, non-convex problems, and demonstrate its use and effectiveness. Using five parameters controlling key aspects of our model, we find that this method is able to converge to regions of high functional similarity with real MEG data, with very few samples given the number of parameters, without getting stuck in local extrema, and while building and exploiting a map of uncertainty defined smoothly across the parameter space. We compare the results obtained using different methods of structural connectivity estimation from diffusion tractography, and find that one method leads to better simulations.

On the mechanical behaviour of PEEK and HA cranial implants under impact loading.

The human head can be subjected to numerous impact loadings such as those produced by a fall or during sport activities. These accidents can result in skull fracture and in some complex cases, part of the skull may need to be replaced by a biomedical implant. Even when the skull is not damaged, such accidents can result in brain swelling treated by decompressive craniectomy. Usually, after recovery, the part of the skull that has been removed is replaced by a prosthesis. In such situations, a computational tool able to analyse the choice of prosthesis material depending on the patient's specific activity has the potential to be extremely useful for clinicians. The work proposed here focusses on the development and use of a numerical model for the analysis of cranial implants under impact conditions. In particular, two main biomaterials commonly employed for this kind of prosthesis are polyether-ether-ketone (PEEK) and macroporous hydroxyapatite (HA). In order to study the suitability of these implants, a finite element head model comprising scalp, skull, cerebral falx, cerebrospinal fluid and brain tissues, with a cranial implant replacing part of the skull has been developed from magnetic resonance imaging data. The human tissues and these two biocompatible materials have been independently studied and their constitutive models are provided here. A computational model of the human head under impact loading is then implemented and validated, and a numerical comparison of the mechanical impact response of PEEK and HA implants is presented. This comparison was carried out in terms of the effectiveness of both implants in ensuring structural integrity and preventing traumatic brain injury. The results obtained in this work highlight the need to take into account environmental mechanical considerations to select the optimal implant depending on the specific patient: whereas HA implants present attractive biointegration properties, PEEK implant can potentially be a much more appropriate choice in a demanding mechanical life style. Finally, a novel methodology is proposed to assess the need for further clinical evaluation in case of impact with both implants over a large range of impact conditions.

A probabilistic atlas of the cerebellar white matter.

Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders.

High resolution whole brain diffusion imaging at 7T for the Human Connectome Project.

Mapping structural connectivity in healthy adults for the Human Connectome Project (HCP) benefits from high quality, high resolution, multiband (MB)-accelerated whole brain diffusion MRI (dMRI). Acquiring such data at ultrahigh fields (7T and above) can improve intrinsic signal-to-noise ratio (SNR), but suffers from shorter T2 and T2(⁎) relaxation times, increased B1(+) inhomogeneity (resulting in signal loss in cerebellar and temporal lobe regions), and increased power deposition (i.e. specific absorption rate (SAR)), thereby limiting our ability to reduce the repetition time (TR). Here, we present recent developments and optimizations in 7T image acquisitions for the HCP that allow us to efficiently obtain high quality, high resolution whole brain in-vivo dMRI data at 7T. These data show spatial details typically seen only in ex-vivo studies and complement already very high quality 3T HCP data in the same subjects. The advances are the result of intensive pilot studies aimed at mitigating the limitations of dMRI at 7T. The data quality and methods described here are representative of the datasets that will be made freely available to the community in 2015.

Effects of image reconstruction on fiber orientation mapping from multichannel diffusion MRI: reducing the noise floor using SENSE.

PURPOSE: To examine the effects of the reconstruction algorithm of magnitude images from multichannel diffusion MRI on fiber orientation estimation. THEORY AND METHODS: It is well established that the method used to combine signals from different coil elements in multichannel MRI can have an impact on the properties of the reconstructed magnitude image. Using a root-sum-of-squares approach results in a magnitude signal that follows an effective noncentral-χ distribution. As a result, the noise floor, the minimum measurable in the absence of any true signal, is elevated. This is particularly relevant for diffusion-weighted MRI, where the signal attenuation is of interest. RESULTS: In this study, we illustrate problems that such image reconstruction characteristics may cause in the estimation of fiber orientations, both for model-based and model-free approaches, when modern 32-channel coils are used. We further propose an alternative image reconstruction method that is based on sensitivity encoding (SENSE) and preserves the Rician nature of the single-channel, magnitude MR signal. We show that for the same k-space data, root-sum-of-squares can cause excessive overfitting and reduced precision in orientation estimation compared with the SENSE-based approach. CONCLUSION: These results highlight the importance of choosing the appropriate image reconstruction method for tractography studies that use multichannel receiver coils for diffusion MRI acquisition.

Bi-component semiconductor oxide photoanodes for the photoelectrocatalytic oxidation of organic solutes and vapours: a short review with emphasis to TiO2-WO3 photoanodes.

The use of binary semiconductor oxide anodes for the photoelectrocatalytic oxidation of organic species (both in solution and gas phase) is reviewed. In the first part of the review, the principle of electrically assisted photocatalysis is presented, the preparation methods for the most common semiconductor oxide catalysts are briefly mentioned, while the advantages of appropriately chosen semiconductor combinations for efficient UV and visible (vis) light utilization are highlighted. The second part of the review focuses on the discussion of TiO(2)-WO(3) photoanodes (among the most studied bi-component semiconductor oxide systems) and in particular on coatings prepared by electrodeposition/electrosynthesis or powder mixtures (the focus of the authors' research during recent years). Studies concerning the microscopic, spectroscopic and photoelectrochemical characterization of the catalysts are presented and examples of photoanode activity towards typical dissolved organic contaminants as well as organic vapours are given. Particular emphasis is paid to: (a) The dependence of photoactivity on catalyst morphology and composition and (b) the possibility of carrying out photoelectrochemistry in all-solid cells, thus opening up the opportunity for photoelectrocatalytic air treatment.

Optimal conditions for the direct RP-HPLC determination of underivatized amino acids with online multiple detection.

The combined use of a dual-UV detector as well as a fluorimetric and a multielectrode electrochemical detector (equipped with a dual electrode, consisting of a conventional size 3 mm diameter glassy carbon electrode (GCE) and of a pair of 30 µm thick carbon microfibers) is proposed for the detection of the following 15 underivatized amino acids: L: -histidine (his), L: -cysteine (cys), creatine (crn), S-methyl-L: -cysteine (me-cys), DL: -homocysteine (hcy), L: -methionine (met), beta-(3,4-dihydroxyphenyl)-L: -alanine (dopa), L: -tyrosine (tyr), DL: -m-tyrosine (m-tyr), L: -a-methyl-dopa (me-dopa), L: -phenylanine (phe), DL: -alpha-methyltyrosine (me-tyr), 5-hydroxy-tryptophan (5htp), 3-nitro-L: -tyrosine (NO(2)Tyr) and L: -tryptophan (trp), as well as of two dipeptides: L: -cystathionine (cysta), L: -carnosine (car), and of creatinine (cre). A multilinear solvent (acetonitrile) gradient elution program, determined by a simple optimization algorithm, is required for the efficient reversed phase separation of the above mixture of 18 solutes within 27 min at a flow rate of 1.0 mL/min and at 25°C.

Anodic stripping voltammetry at a new type of disposable bismuth-plated carbon paste mini-electrodes.

A new type of disposable carbon paste mini-electrodes (CPmEs), with dimensions in the 50-300 microm range, have been fabricated by heat-shrinking the end-tip of plastic micropipette tips and filling them with carbon paste. The CPmEs have been characterized by microscopic and electrochemical means and tested as substrates for in situ plated Bi film electrodes (BiF-CPmEs), used in the determination of heavy metals by square wave anodic stripping voltammetry (SWASV). It was found that this new class of CPmEs combines the advantages of carbon paste electrodes (readily renewable surface and high surface area) with those of near-microelectrode behaviour (no stirring or electrolyte excess needed). During SWASV experiments in unstirred Pb(II) and Cd(II) solutions well-shaped stripping peaks were obtained whose height varied linearly with analyte concentration in the wide 1x10(-8) to 10(-6) M range, both in acetate buffer and unbuffered solutions. Under optimal conditions detection limits of 8x10(-10) and 1.3x10(-9) M were achieved for Pb(II) and Cd(II), respectively and in a trial application, these metal ions have been determined in a spiked tap water sample using a BiF-CPmE.

Anodic stripping voltammetry at in situ bismuth-plated carbon and gold microdisc electrodes in variable electrolyte content unstirred solutions.

Carbon and gold microdisc electrodes (30 and 10 microm, respectively) have been tested as substrates for in situ bismuth film plating from unstirred solutions of variable acetate buffer content and were subsequently used in the anodic stripping voltammetry determination of Pb(II) and Cd(II) ions. The effects of Bi(III) concentration, analyte accumulation time, stirring as well as supporting electrolyte content have been studied. Under optimal conditions good voltammetric responses were obtained by means of square wave anodic stripping voltammetry in unstirred analyte solutions of 5 x 10(-8) to 10(-6)M, even in the absence of added buffer. In an indicative application, Pb(II) ion levels were determined in tap water using bismuth-plated carbon microdisc electrodes.

Study on the electrochemical detection of the macrolide antibiotics clarithromycin and roxithromycin in reversed-phase high-performance liquid chromatography.

The optimal conditions of the amperometric detection of the macrolide antibiotics clarithromycin and roxithromycin were found by cyclic voltammetric studies and HPLC-electrochemical detection responses obtained in different temperatures (25.5-60 degrees C) and different but almost isoelutropic binary, ternary and quaternary mixtures of aqueous buffer (pH 7), methanol, acetonitrile and isopropanol. These conditions were also proved to be applicable for the quantitative detection of clarithromycin in human plasma using roxithromycin as an internal standard and vice versa. It was demonstrated that increased attention has to be paid to eluent composition and column temperature to ensure sensitive and reproducible electrochemical responses as well as regularly shaped peaks for both macrolides tested.

Childhood lawn dart injuries. Summary of 75 patients and patient report.

Lawn dart injuries account for an estimated 675 emergency department visits per year. Seventy-six patients are described herein. The victims ranged from 1 to 18 years of age and were predominantly male (male to female ratio is 3.1:1). The most common sites of injury were head (54%), eye (17%), and face (11%). Hospitalization was required for 54% (41/76) of these patients. Sequelae included unilateral blindness and brain damage. The case fatality rate was 4%. The extent of a head injury was not always clinically apparent at the initial presentation and should be promptly defined by computed tomographic scan. Despite the recent ban on the sale of lawn darts, there remain an estimated 10 to 15 million sets of lawn darts in the homes of Americans. Pediatricians should encourage parents to discard all lawn darts.

Alpha-streptococcal septicemia in leukemic children treated with continuous or large dosage intermittent cytosine arabinoside.

During a 2-year period after the introduction of an intensive chemotherapeutic protocol, alpha-hemolytic streptococci accounted for 75% of all episodes of sepsis among children with acute nonlymphocytic leukemia at our institution. Only one case had occurred in the previous 8 years. Fourteen of 15 episodes of streptococcal sepsis occurred after therapy with either continuous or large dosage intermittent cytosine arabinoside. Eleven episodes occurred at two specific treatment points. Septic episodes were complicated by shock (2 of 15), encephalopathy (2 of 15), pneumonia (3 of 15) and death (1 of 15). Oral mucosal lesions may provide a portal of entry for alpha-hemolytic streptococci. These data suggest that children receiving continuous or large dosage intermittent cytosine arabinoside for treatment of acute nonlymphocytic leukemia may be at increased risk for alpha-hemolytic streptococcal sepsis. Empiric antimicrobial therapy in these children when febrile and neutropenic should include antibiotics effective against alpha-hemolytic streptococci.

Differentiation between postoperative scar and recurrent disk herniation: prospective comparison of MR, CT, and contrast-enhanced CT.

Twenty-five symptomatic postlumbar surgery patients had findings on lumbar spinal noncontrast CT that were equivocal for distinguishing recurrent disk herniation from postoperative epidural fibrosis (scar). Contrast-enhanced CT and lumbar MR imaging were performed to differentiate these two conditions. Of the 14 levels, surgically explored, the diagnosis of scar or recurrent disk herniation was correct with contrast-enhanced CT at 10 levels and with MR imaging at 11 levels. At the levels operated on less than 2 years prior to MR imaging, scar more frequently demonstrated intermediate than low signal intensity. Scar older than 2 years most often showed low signal intensity. These preliminary findings suggest that MR may be useful in differentiating postoperative fibrosis from recurrent disk herniation in a significant proportion of patients whose unenhanced CT scans are equivocal.

The anatomy of free paper sessions.

The interaction between speakers, audience, and chairmen was studied by 13 investigators during a medical meeting at which 356 free papers were given before a total audience of 2483 in 48 sessions. A protocol was used to score 21 questions relating to the presentation, 15 to the chairman of the session, and nine to the audience. Many speakers made technical faults in presentation and their use of slides. Most chairmen failed to comply with simple rules of procedure and with the expectations of speakers and audience. The interest of the audience was affected by the performance of speakers and chairman. Speakers should pay more attention to the technique of presentation, and organising committees of medical meetings should provide instructions to both speakers and chairmen.