Pyramidal neurons of the neocortex display a wide range of synchronous EEG rhythms, which arise from electric activity along the apical dendrites of neocortical pyramidal neurons. Here we present a theoretical description of oscillation frequency profiles along apical dendrites which exhibit resonance frequencies in the range of 10 to 100 Hz. The apical dendrite is modeled as a leaky coaxial cable coated with a dielectric, in which a series of compartments act as coupled electric circuits that gradually narrow the resonance profile. The tuning of the peak frequency is assumed to be controlled by the average amplitude of voltage-gated outward currents, which in turn are regulated by the subthreshold noise in the thousands of synaptic spines that are continuously bombarded by local circuits. The results of simulations confirmed the ability of the model both to tune the peak frequency in the 10–100 Hz range and to gradually narrow the resonance profile. Considerable additional narrowing of the resonance profile is provided by repeated looping through the apical dendrite via the corticothalamocortical circuit, which reduced the width of each resonance curve  to approximately 1 Hz. Synaptic noise in the neural circuit is discussed in relation to the ways it can influence the narrowing process. The pyramidal neuron, with its relatively long dendrite that extends upward from the top of the soma, is the main excitatory neuron and most numerous type of neuron found in the neocortex resonance denotes the ability of a system to oscillate most strongly at a particular frequency.Electrical brain rhythms, particularly synchronized oscillations generated by the pyramidal neurons, are measured as encephalograms (EEGs), and are believed to be related to a wide variety of cognitive functions Resonance activity apparently can arise from noise in neural networks in a variety of ways, ranging from the stochastic resonance produced by a moderate level of synaptic noise that enhances subthreshold signals, e.g., Apparently, transient alterations in synaptic function on the dendrites of the waking animal are continually being initiated by local circuit background activity on dendritic spines, which produce subthreshold membrane activity. Alterations are produced by locally produced action potentials and backpropagating action potentials. The finding The purpose of the present paper is to increase our understanding of the mechanisms by which the dendritic membrane can become tuned to a specific narrow band of frequencies by describing a model of the transfer of electrical energy along the apical dendrite of a neocortical pyramidal neuron. As current pulses move down the apical dendrite, they are influenced by the conductive and capacitive elements of the anisotropic membrane . The progressive narrowing of resonance in the present model of the neocortical apical dendrite is based on the surface impedance theory formulated by Delogne The vertical shaft of the typical human neocortical apical dendrite is modeled here as a series of 6 compartments, as shown in The input from the thalamic principal neuron to the first compartment is located at the distal region of the Layer 5 apical dendrite for all neocortical minicolumns except for minicolumns located in the primary sensory areas, where the input from the thalamic principal neuron is mainly in the mid region of the Layer 5 pyramidal neuron, but with some inputs at the distal region The instantaneous movement of charges is represented in Each circuit compartment contains an active voltage-gated outward conductance, The present formulation may be considered a variation of traditional cable theory The approach taken here modifies the circuit of the traditional cable model by replacing the inductance (L) element with a capacitive element that is directed along the outer surface, longitudinal to current, so that the circuit now contains two kinds of capacitive elements: the non-linear surface capacitance, rane see . Energy Delogne's theory The apical dendrite model we have proposed has a single peak value in the band-pass characteristic not because of any energy exchanges back and forth between inductance L and capacitance C as in electric circuit theory. A resonance or peak amplitude in the transfer impedance of the neuron is created by the way the electric energy divides between the surface and membrane capacitive and conductive elements as a function of frequency. At low frequencies, capacitance tends to block current flow and at high frequencies capacitance tends to act as a short.The horizontal capacitance For the single compartment, the derived steady-state complex transfer impedance is: where andThe parameters, Equation (1) contains expressions for two different capacitances: The dynamic characteristics of this network model can be specified by either its voltage transfer function, The sheath geometry for the classical leaky cable involves a cylindrical outer surface defined by a two-layer construction: a conducting layer on one side and a dielectric layer on the other side. Holes (channels) exist through the surface allowing current flow from inside the cable to outside or in the opposite direction. The surface impedance representation of the current and voltage boundary condition for a leaky cable is assumed to be approximately equivalent to the dendrite outer surface impedance boundary in the range of neuronal resonant frequencies of our paper by symmetry. The effect of attenuation or resistivity (conductivity) in Equation (7), is given by the propagation constant or wave number for the classical neuron cable model The surface transfer admittance derived from the Delogne leaky cable theory where Using the definition of the classical cable propagation constant, and the well-known formulas for the intracellular impedance, andandwhere The electrical theory of leaky cables applied here to the dendritic segment provides a way to consider the effect of coupling between longitudinal currents  and radial membrane currents (across the membrane). If we consider the charge per unit length on each of two concentric cylindrical coaxial capacitor surfaces, the per unit length capacitance of a coaxial cable is given by Equation (11) The many radial leak paths of the membrane containing high conductivity fluid greatly increase the membrane conductivity over that of the axon membrane. Although many kinds of conductances exist in the dendritic membrane tric see . The eletric see . Axon meTo observe the operation of the one-compartment circuit over the 10–100 Hz range where most of the EEG measurements in the literature are located, we estimated the transfer impedances that showed peak values at 20, 40, 60, and 80 Hz. Using the circuit parameters assumed for the present model, we obtained maximum impedance amplitude values for these 4 frequency locations of 2.5369, .46009, .13223, and .04952 The four transfer impedance amplitude curves shown in where To illustrate the amplitude calculation of the impedance values shown in 0 Hz see .The corresponding phase angles calculated from Equation (1) are shown in When we insert into Equation (13) the same vely see .The impedance amplitude curves, shown in The impedance phase curves, shown in in vitro experiment with rats The general characteristics of the impedance amplitude and phase curves of the present model, shown in The amplitude curves shown in To achieve a narrow, peaked resonance curve, we extend the present single compartment model to a 6-compartment model, with the added feature that the pulse train is recycled repeatedly through the 6 compartments by way of the thalamus within the corticothalamic circuit. Both the single compartment and the looping multiple-compartment models assume that the average level of the radial conductance, Although transmembrane ion channels are distributed non-uniformly over a segment of dendritic membrane The magnitude of the impedance transfer functions of the cascade-loop model, plotted as percent of maximum voltage for 20, 40, 60, and 80 Hz peak frequencies, are shown in According to the model, the peak frequency of the impedance transfer function is shifted upward or downward by varying the level of the total output conductance, which in turn is influenced by the tonic voltage level maintained inside the dendrite by the subthreshold synaptic activity at the hundreds of local spines. The area of the resonance curve around the peak is narrowed by successive electrical operations in the compartments through which the pulse travels as it makes its way toward the soma. As more compartments are traversed the resonance peak becomes more sharply defined.Two aspects of resonance tuning are treated in this paper: (a) the selection of the peak frequency of the resonance curve, and (b) the sharpening of the resonance curve around the peak frequency.(a) Selective activity is indicated by the finding that the impedance transfer function exhibits a peak, which suggests that only one compartment of the apical dendrite model is needed to exhibit some degree of selective filtering over the total range of frequencies of an injected input. Although the peak in the single-compartment case is weakly defined here, the peak becomes more noticeably narrowed when the compartment operations are repeated through more compartments. Thus when the current containing a range of frequencies is passed to the next compartment, the voltage of some frequencies will be larger than that of other frequencies. As mentioned in the previous section, the physical basis hypothesized for the selection of the (peak) resonance frequency is the outward conductance of potassium ions. A particular value of outward conductance is produced by a corresponding level of voltage on the inside surface of the membrane. This level of internal voltage is maintained by the ongoing subthreshold synaptic activity in local spines, which in turn is produced by pulses from axons of the local cortical circuitry. The local circuitry of the cortex is assumed to be noisy, owing to its complex circuitry and the firing characteristics of the constituent neurons. The source or sources that regulate the level of this background noise apparently are not yet known in detail. However, it would seem that the noise level for a specific minicolumn (or for a column cluster of minicolumns) should differ from the noise level of minicolumns serving other functions. For example, the ambient background noise level for minicolumns involved in processing the color red should exhibit a different noise level than the minicolumns involved in processing the square shape of an object. In this way the corticocortical circuits that connect Layer 2/3 pyramidal neurons of a group of minicolumns can function somewhat independently of the noise level of minicolumn local circuits, once the local noise level selects the resonance frequency of the participating pyramidal neurons. The amplitude of the noise of a particular minicolumn will, of course, exhibit a variance, and the size of this variance is expected to affect the sharpness of the resonance function.(b) Sharpening activity, shown in In the search for experimental evidence supporting the existence and function of surface capacitance, While it is recognized that noise is added to the resonance processing within the pyramidal neuron itself, we assume here that the level of that noise is small relative to the level of noise added to the resonance processing by synapses. The issue of synaptic noise in the present model can be separated into the noise produced in two different places in the cascade-loop model of resonance tuning: the ambient noise in the thousands of spines along the apical dendrite shaft which produce subthreshold activation of neighboring conductance channels , and the noise at the synapses in the corticothalamic circuit which enables output current pulses from the dendritic compartments to loop back to the apical dendrite. Many hundreds of spines dot the apical dendrite , as well as the synapses of the principal cell axon on the apical dendrite of the cortical pyramidal cell. Additional synapses to be considered contact the corticothalamic loop from other sources. They include the important synapses by which ascending afferent fibers contact the thalamus en route to the primary sensory cortical areas. For the higher cortical areas, both ascending fibers from lower areas and descending fibers from frontal cortical areas make synaptic contacts with the thalamus see . SynaptiIf the traditional view of noise is applied to the workings of the present model, then all of the synapses under consideration, especially the synapses in the corticothalamic circuit, produce a significant level of noise that tends to flatten the shape of the resonance curve. While every cycle of the corticothalamic circuit adds noise to flatten the shape of the profile of the resonance curve, the next cascade through the apical dendrite compartments narrows the shape of the profile of the resonance curve. If the total noise in the corticothalamic loop is sufficiently large relative to the number of dendritic compartments, then the resonance curve cannot be narrowed to the maximum asymptotes shown in The purpose of the single compartment model simulation is to demonstrate resonance in the apical dendrite by generating four resonance curves, corresponding to peak resonant frequencies of 20, 40, 60, and 80 Hz. To simulate the operations of a segment of the Layer 5 apical dendrite, we employ here the assumed equivalent circuit in a single compartment see . The choTo calculate the transfer impedance, ment see , the expWe now consider the way that the multiple compartment model could tune an apical dendrite to narrow its resonance curve around a particular peak frequency. For the model, we select a segment of the apical dendrite 1200 The decrease in The excitatory input conductance to the nth compartment (At the end of the first compartment, which states that the transfer impedance of that compartment circuit, so that, in general,.The cascading operations across the A cascade through the 6 compartments produces an array of new impedances across the frequency range. These impedance values are sent back to the first compartment via the corticothalamic loop see , and pro


The traditional surgical treatment for abdominal aortic aneurysm (AAA) is now well codified in vascular surgery with a perioperative mortality rate that has gradually declining in recent years. The introduction of endovascular techniques has led the indications for surgery to be reviewed. The results of surgery in patients over eighty are fairly well defined: it is encoded that age affects only a small part of the immediate results in terms of overall mortality, while it is a significant factor in increasing rates of perioperative major morbidity, in particular cardiac and respiratory diseases. The purpose of this article is to assess the octogenarian patients who are not candidates for treatment with endoprosthesis.The characteristics of the proximal neck, distal and size influence the feasibility of enablers and results of endovascular treatment. All patients who do not respect these features are handled by us with traditional surgery. The high prevalence of ischemic heart disease in patients with AAA is a major cause of morbidity and mortality  in the surgical treatment of AAA .Literature data show that if coronary angiography is performed routinely in patients with AAA awaiting surgery, the frequency of hemodynamically significant stenosis varies from 46 to 75%.  For the reasons that all patients, twice in our experience can not be treated by endovascular undergo coronary angiography before surgery for AAA.In our series, since 2002, we have operated on 560 patients of which 282 are of AAA ultra octogenarians.Of these, 224 have been processed with endoprosthesis and 58 to surgical repair of aortic graft. 100% of those operated with traditional surgery had a short proximal neck, in 70% with the involvement of a renal artery aneurysm. 42% of all patients had a coronary heart disease that was treated preoperatively with coronary stents. Among the octogenarians the operative mortality of patients undergoing surgical repair for AAA was 4%.The advent of endoprotesis has certainly improved the survival rate and morbidity of elderly patients with risk of AAA rupture. A selection of the patients, careful study of cardiac risk and treatment of coronary artery disease and carotid artery before surgery are prerequisites to reduce perioperative complications.


Attention Deficit/Hyperactivity Disorder (ADHD) is considered as a model of neuro-developmental cognitive function. ADHD research previously studied mainly males. A major biological distinction between the genders is the presence of a menstrual cycle, which is associated with variations in sex steroid hormone levels. There is a growing body of literature showing that sex hormones have the ability to regulate intracellular signaling systems that are thought to be abnormal in ADHD. Thus, it is conceivable to believe that this functional interaction between sex hormones and molecules involved with synaptic plasticity and neurotransmitter systems may be associated with some of the clinical characteristics of women with ADHD. In spite of the impact of sex hormones on major neurotransmitter systems of the brain in a variety of clinical settings, the menstrual cycle is usually entered to statistical analyses as a nuisance or controlled for by only testing male samples. Evaluation of brain structure, function and chemistry over the course of the menstrual cycle as well as across the lifespan of women  is critical to understanding sex differences in both normal and aberrant mental function and behavior. The studies of ADHD in females suggest confusing and non-consistent conclusions. None of these studies examined the possible relationship between phase of the menstrual cycle, sex hormones levels and ADHD symptoms. The menstrual cycle should therefore be taken into consideration in future studies in the neurocognitive field since it offers a unique opportunity to understand whether and how subtle fluctuations of sex hormones and specific combinations of sex hormones influence neuronal circuits implicated in the cognitive regulation of emotional processing. The investigation of biological models involving the role of estrogen, progesterone, and other sex steroids has the potential to generate new and improved diagnostic and treatment strategies that could change the course of cognitive-behavioral disorders such as ADHD. Behavioral, biochemical, and physiological data in animals demonstrate that gonadal steroid hormones estrogen, progesterone and testosterone have an effect on behavior and modulate neuronal activity  experience regular menstrual cycle from menarche to menopause, whereas the rest have irregular cycles , (unipolar) postpartum depression, perimenopausal depression, and bipolar disorder  studies have investigated the impact of fluctuating sex hormone levels during the menstrual cycle on the interplay between emotion and cognition in healthy regularly cycling women. This lack of knowledge is remarkable, considering the evidence for major emotional disorders occurring specifically during normal hormonal swings in the lifespan of women. A recent review of the literature by As with many neurodevelopmental disorders, the prevalence of attention deficit/hyperactivity disorder (ADHD) differs in males and females , and external hormonal use . In spite of the impact of sex hormones on major neurotransmitter systems of the brain in a variety of clinical settings, the menstrual cycle is usually entered to statistical analyses as a nuisance regressor (Lonsdorf et al., We suggest that the menstrual cycle should be considered as a modulating factor when examining cognitive response to emotional information in women. Furthermore, with the introduction of sensitive tests to measure cognitive performance and imaging techniques to visualize brain morphology and study its neurochemistry, it is now becoming possible to carefully analyze cognitive performance in women by their menstrual cycle phase, or current hormonal status. This may lead to better understanding of the sex hormone impact on women’s brain in health as well as in ADHD and may resolve the inconsistency of the findings in women with ADHD.


Fillet flaps are commonly used to cover skin defects after trauma or tumors, especially in the extremities -5.We report four patients operated in the last three years, for lesions of the ear, invading the post auricular skin and infiltrating into the scalp.On examination these ulcerating lesions had the clinical appearance of deeply infiltrating basal cell carcinoma. Surgery was performed under general anaesthesia.After resection was performed with 1 cm skin margins, down and including the temporal fascia, the clear anterior skin surface of the upper pole of the ear was freed by its internal cartilaginous skeleton. The obtained fillet flap of the homolateral upper ear pole was raised and reflected posteriorly to cover the wound completely or partially. When needed, a split skin graft was added to the reconstruction.Histology gave the confirmation of the diagnosis and indications on the radicality in the operated patients. The cosmetic result was satisfactory. Follow up at a mean 6 months showed no recurrence.Several possibilities for the coverage of scalp defects have been reported, includiWe describe the use of fillet of pinna flap to cover periauricular scalp defects. We are not aware of any report of this type of flap to cover defects following tumour resection.The main advantages of the fillet of pinna flap are its durable coverage, colour match of the skin and absence of a donor site defect. In our patients, flaps were composed of healthy tissue which otherwise would have been discarded in the resection. In our opinion, fillet of pinna flaps can be used to cover the periauricular scalp defects when the auricular skin is clear and not been invaded by the lesion.


The structure of the hydrogen bond network is a key element for understanding water's thermodynamic and kinetic anomalies. While ambient water is strongly believed to be a uniform, continuous hydrogen-bonded liquid, there is growing consensus that supercooled water is better described in terms of distinct domains with either a low-density ice-like structure or a high-density disordered one. We evidenced two distinct rotational mobilities of probe molecules in interstitial supercooled water of polycrystalline ice . Here we show that, by increasing the confinement of interstitial water, the mobility of probe molecules, surprisingly, increases. We argue that loose confinement allows the presence of ice-like regions in supercooled water, whereas a tighter confinement yields the suppression of this ordered fraction and leads to higher fluidity. Compelling evidence of the presence of ice-like regions is provided by the probe orientational entropy barrier which is set, through hydrogen bonding, by the configuration of the surrounding water molecules and yields a direct measure of the configurational entropy of the same. We find that, under loose confinement of supercooled water, the entropy barrier surmounted by the slower probe fraction exceeds that of equilibrium water by the melting entropy of ice, whereas no increase of the barrier is observed under stronger confinement. The lower limit of metastability of supercooled water is discussed. Several water anomalies with deep implications in biology, atmospheric phenomena, geology, and food technology are rooted in the supercooled liquid state The different viewpoints on supercooled water can be partitioned into two broad classes: mixture/interstitial models and distorted hydrogen bond or “continuum” models The above discussion pointed out that regions of ice-like supercooled water are expected by mixture models of water In parallel with several numerical studies, e.g. At ambient pressure the supercooled regime of water ranges between the glass transition temperature In polycrystalline ice liquid water is localized where three grain meet in channels, or veins, that generally extend along the whole length of the grain edge. Four veins meet in a node (pocket) at a four-grain intersection, thereby forming a sponge-like, interconnected network of veins known as the vein system. The network was evidenced by experiments Dimensional arguments lead to the conclusion that the volume fraction (f) of water with respect to ice in the vein system has the expression The experiments show that the size of the ice grains decreases by increasing the cooling rate From the above discussion it follows that the liquid fraction in polycrystalline ice close to One may resort to the different character of the vein size (controlled by the thermodynamics) and the grain size  to control the degree of confinement of the liquid fraction in ice/water mixtures. Consider two ice-water mixtures with different polycrystallinity and equal temperature It is worth noting that increasing the confinement of water close to a hydrophilic surface like ice is equivalent to a pressure (or density) increase In a previous paper we reported evidence of two distinct rotational mobilities of probe molecules (spin probes) in interstitial supercooled water of polycrystalline ice The major conclusions of the study, which is presented and discussed below, are:the S fraction of the spin probes is embedded in regions of QRW water with ice-like structure ,the ice-like environment is suppressed in the liquid fraction of SC ice/water mixtures .We studied the rotational motion of the polar nitroxide molecule TEMPOL (spin probe) in the interstitial liquid water of polycrystalline ice by using the Electron Spin Resonance (ESR) spectroscopy This finding is consistent with the stronger water confinement in the SC sample than in the QRW sample – where the lineshape collapse was never observed – combined with the shrinkage of the reservoirs where TEMPOL is trapped when departing from the melting point faster the reorientation, the narrower the line. Inspection of faster in SC water below higher temperature Apart from the previous case, the ESR lineshapes in one adjustable parameter describes its reorientation in a given environment no signature of ice melting has been detected in QRW water while crossing To gain more quantitative insight, we fitted the ESR lineshape of TEMPOL by using the numerical methods detailed elsewhere faster than in QRW water (as hinted by is same activated process as that of the equilibrium region (is driven by the not show the signature of the fragile-to-strong dynamic crossover (FSC) temperature at does Since TEMPOL links up with the HB network of water average environment, denoted by FS  were prepared by direct exposition to liquid helium  and slow (S) fractions of TEMPOL, with weights


Distal humerus fractures may range from a simple extra-articular fracture pattern to a complex pattern, involving extensive destruction of the articular surface with comminution and bone loss in the metaphyseal-diaphyseal junction of the bone.The management decision in the younger patient requires complete anatomical reconstruction and early active range of motion. Different approaches to the distal humerus will be discussed, as will be different fixation methods. I will also present relevant clinical cases and outline the known outcomes of these fractures.In the elderly with osteoporotic fractures especially those with preexisting arthritis, there is an emerging trend for primary total elbow replacement. The outcomes of such replacement have been shown to be comparable to those of total elbow replacement in arthritis. However, there have been a few complications reported in the literature and this method is best reserved for complex comminuted distal humerus fractures in patients with significant osteoporosis and those above the age of 70.I will also discuss complex fracture dislocations of the elbow joint in terms of the management decisions and outcomes of these difficult problems.


Microstructural disturbances develop in the wall of vessels in patients with mild traumatic brain injuries (TBI).The purpose of our research was to detect the regularities of changes of hemodynamics and reactivity of cerebral circulation in patients with consequences of mild traumatic brain injuries by using the method of Doppler ultrasonography with hyper-and hypocapnic tests.We examined 62 patients with consequences of mild TBI. The control group consisted of 20 healthy people. Doppler ultrasonography with hyper-and hypocapnic tests were carried out according to the standard method.Conducting Doppler ultrasonography with hyper-and hypocapnic tests in the patients with consequences of TBI we detected that coefficient of reactivity was 1.11±0.07. The insignificant asymmetry of bloodflow which increased after hyper- and hypocapnia was observed in the patients (82%). An early development of atherosclerotic lesion of cerebral vessels in the form of hemodynamic insignificant atherosclerotic plaques of the walls of cerebral vessels was observed (73%). We detected paradoxical reaction of cerebral vessels in 40 patients when hyper-and hypocapnic tests were being held.The data obtained confirm the changes of reactivity of cerebral vessels towards the decrease of linear velocity of bloodflow in the patients with consequences of mild TBA. The detected paradoxical reaction of vessels which was observed when we used hyper-and hypocapnic tests, is the consequence of the decrease of elasticity of vessels walls as a result of microstructural disturbances of vessels, an early development of atherosclerotic changes in vessels and the manifestation of a long-term angiospasm.No conflict of interest.


Plaster casts of individual patients are important for orthodontic specialists during the treatment process and their analysis is still a standard diagnostical tool. But the growing capabilities of information technology enable their replacement by digital models obtained by complex scanning systems.This paper presents the possibility of using a digital camera as a simple instrument to obtain the set of digital images for analysis and evaluation of the treatment using appropriate mathematical tools of image processing. The methods studied in this paper include the segmentation of overlapping dental bodies and the use of different illumination sources to increase the reliability of the separation process. The circular Hough transform, region growing with multiple seed points, and the convex hull detection method are applied to the segmentation of orthodontic plaster cast images to identify dental arch objects and their sizes.The proposed algorithm presents the methodology of improving the accuracy of segmentation of dental arch components using combined illumination sources. Dental arch parameters and distances between the canines and premolars for different segmentation methods were used as a measure to compare the results obtained. A new method of segmentation of overlapping dental arch components using digital records of illuminated plaster casts provides information with the precision required for orthodontic treatment. The distance between corresponding teeth was evaluated with a mean error of 1.38% and the Dice similarity coefficient of the evaluated dental bodies boundaries reached 0.9436 with a false positive rate  In the fields of orthodontics and dentofacial orthopaedics, the optimal timing with regard to the patient’s age and skeletal maturity is just as important as identification of the most appropriate treatment process. Depending on his or her actual age, it is critical to identify the growth periods that provide an opportunity to correct the existing dentofacial irregularities while minimizing the potential risks of the orthopedics intervention using dental arch analysis. Multidisciplinary dental care  and therAlthough dental casts have been used for diagnosis and treatment planning , 3 in vaThe aim of this paper is to analyse digitized dental plaster casts –9 by a cFor more than a century, traditional film radiographs were used at most dental clinics before digital dental radiography was firstly introduced  in the lThe latest developments in computer technology enable creating electronic tools that can benefit many areas of medicine, surgery and dentistry –15. ImagDevices for the digital imaging of dental casts include 3D scanners, 3D printers, and digital cameras in general. For the purpose of this paper, the 2D digital images of a standard plaster cast were acquired by a digital camera using different directions of illumination sources to obtain images with different shadow sizes related to the shape of the plaster cast.The experimental environment included the camera placed at a fixed position above the observed orthodontic plaster cast. The source of illumination was installed at the side of the plaster cast to obtain an image with a shadow and reflection to improve the location of the boundary of the object. Instead of using a single image, a series of images was acquired and combined for the following segmentation process. The location of the illumination source was defined by its azimuth  image quality. The noise of the image negatively affects the quality of the image, changing the true grey-level values of each its pixel. Such noise can be caused by a number of factors, including image acquisition conditions, illumination level, positioning of illumination sources, and scene environment.The initial analysis of the image noise components allows designing the appropriate filter to reduce the noise and to keep the desired information. Noise components of the digital camera (using CCD or CMOS sensors) can be classified into two main categories: the fixed pattern noise caused by sensor non-uniformities and temporal noise. Temporal noise is a non-ideality noise in an image sensor which varies randomly over time. In fact, this type of noise varies from frame to frame and is independent across pixels. The sources of noise related to the camera include photon shot noise, dark current, readout noise, reset noise, and quantization noise.The Wiener filter was applied as a type of low-pass filter  that adaThe Wiener filter output a with the median value of all The median filter was used in image processing as a robust filter , 19 thatThe determination of the curvature and location of circular objects in an (orthodontic) image are important tasks  in machiThe circular Hough transform used in the present paper obtains satisfactory results in the detection of circle patterns within an image  in noisyThe segmentation –26 of anThe proposed algorithm is based upon the region growing method using multiple seed points for segmentation of orthodontic images based on partitioning of an image into regions –30 usingQ connected sub-regions Pixels that have similar properties form a region and are grouped together. The purpose of image segmentation  is to diThe region growing method is initiated with the appropriate selection of a set of seed points. When there exists a priori information about the image properties, such starting points can be defined directly. Otherwise, selected properties should be evaluated for each pixel and after the initial clustering process, seeds can be defined in the centroids of the obtained clusters. The growing starts from the initial seed points and using predefined criteria makes it possible to group pixels with similar properties into larger regions.The iteration process of the region-growing method can be stopped in case all pixels are distributed into regions according to the predefined criteria but some additional conditions can be added, such as region sizes or their shapes. According to the threshold values selected and the sensitivity, the extracted region may grow over the actual region boundary. The suitable selection of seed points, stopping rules, thresholding, and sensitivity  are veryT components in two-dimensional space. The associated morphology algorithm can then be used to define the convex hull by kth convex hull component for The region growing method applied to one object results in several sub-areas. Their merging can be done using computational geometry and detection of a convex hull cument}Z , 36 compThe separation of two connected neighbouring regions when their common boundaries were removed during data processing is an important issue in image analysis and machine vision applications. The identifying of a common boundary between two regions or two overlapping objects is usually challenging, as one segment is incorrectly detected by the segmentation process. Several studies and algorithms  have beeApplication of a number of morphological operators, such as dilation performed for boundary extraction, filling the holes to remove unwanted regions in the binary image, and shrinking for reducing the objects on the boundary to a single point. Dilation aims to expand objects in a binary image  where thThe application of boundary tracing of two connected neighbouring regions and smoothing of the traced boundary by a moving average filter. In the binary image, the foreground pixels are labelled by ‘one’ and the background pixels are labelled by ‘zero’  so that Calculation of the second derivative at each point on the smoothed boundary of two connected neighbouring regions.Determination of specific zones that contain the intersection points of two connected regions based on the second derivative that are situated inside of the object.Evaluation of the absolute extreme of the two zones obtained in the previous step which will mark the position of the intersection points of the two connected regions.Figure In this paper, we propose identifying the common boundaries of two connected neighbouring regions for orthodontic images presented in Figure Image acquisition with the proposed illumination strategy and fusion of image matrices obtained;Wiener and median filtering of image data to reduce their noise components;The use of circular Hough transform to apply local segmentation for individual teeth;Application of the region growing method with multiple seed points to find boundaries of individual sub-images provided by the circular Hough transform;Merging of corresponding sub-areas using computational geometry and convex hull regions to separate overlapping objects as well;Evaluation of dental arch parameters and measures using centers of mass of individual objects detected by the previous segmentation process.Measures obtained are used for evaluation of the effect of the invasive or non-invasive treatment in stomatology. The segmentation process proposed enables semiautomatic evaluation of mass centers of individual objects and more efficient analysis of location of individual teeth.The newly proposed method of dental arch image processing based on separate methods described above consists of the following steps:Figure Figure TP) and false negative (FN) pixels in the positive set, and true negative (TN) and false positive (FP) pixels in the negative set (outside the positive set). The number of pixels belonging to these regions define the following:Sensitivity as the true-positive rate of the correct positive classification in the positive set Specificity as the true-negative rate of the correct negative classification in the negative set Probabilities of false classifications in the positive set  and negative set  Accuracy as the measure of correct classification Jaccard similarity index and Dice coefficient  process –48 with Results of the proposed segmentation process were further analysed by a confusion analysis . Image pThe numerical results presented in Table Similarity measures evaluated for the whole dental arch include the Jaccard index The comparison of selected measures obtained by manual and digital measurements is summarized in Table This paper presented an innovative approach to the segmentation of orthodontic plaster cast images. The proposed method is based on processing the image constructed from separate images acquired with different illumination sources reflecting different edges of the object. The combined image with its increased contrast and enhanced object boundaries is then used for the detection of separate object.The results of segmentation of a digital image of the orthodontic plaster cast by the method proposed in this paper show that the convex hull followed by the separation of two connected objects form effective complementary techniques to improve the segmentation by the region growing method.The illumination from different sides highlights shadows of the object, converting each region into several sub-regions: hence, region growing, based on the application of multiple seed points, is a suitable tool to extract individual bodies. However, the method (1) does not produce satisfactory results in the common boundary of two regions that have similar properties and (2) the identified sub-regions related to the same region are not always recognized as one region.The final evaluation of the segmentation process points to the efficiency of the proposed method with a Dice similarity coefficient of 0.9436 and a mean error of real and estimated distances between corresponding teeth of 1.38%.Further studies will be devoted to further more sophisticated methods based upon three-dimensional convex hulls, used for the separation of individual bodies, as well as to a more detailed analysis of the shapes of the separate dental arch components.


Spinal cord injury and repair is a dynamic field of research. The development of reliable animal models of traumatic spinal cord injury has been invaluable in providing a wealth of information regarding the pathological consequences and recovery potential of this condition. A number of injury models have been instrumental in the elaboration and the validation of therapeutic interventions aimed at reversing this once thought permanent condition. In general, the study of spinal cord injury and repair is made difficult by both its anatomical complexity and the complexity of the behavior it mediates. In this perspective paper, we suggest a new model for spinal cord investigation that simplifies problems related to both the functional and anatomical complexity of the spinal cord. We begin by reviewing and contrasting some of the most common animal models used for investigating spinal cord dysfunction. We then consider two widely used models of spinal deficit-recovery, one involving the corticospinal tracts (CTS) and the other the rubrospinal tract (RST). We argue that the simplicity of the function of the RST makes it a useful model for studying the cord and its functional repair. We also reflect on two obstacles that have hindered progress in the pre-clinical field, delaying translation to the clinical setup. The first is recovery of function without reconnection of the transected descending fibers and the second is the use of behavioral paradigms that are not under the control of the descending fiber pathway under scrutiny. The most commonly used injury paradigms for spinal cord injury are contusions and transections. Contusions are produced by controlled blunt force directed to a portion of the cord, whereas transections consist of selective cuts to all or a portion of the cord. An advantage of contusion methods is that they produce histologically graded and consistent trauma , damage at least two major descending fiber tract systems: the corticospinal tract (CST) and the rubrospinal tract (RST)  CST transection permanently abolishes the down conditioning of the H-reflex in the rat, whereas the ablation of the lateral column has no effect on this type of operant conditioning  and locomotor capacity. We have demonstrated that lesions that affect the integrity of the RST or of its cells of origin in the red nucleus do not produce deficits in whole-limb movement  to RM.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In this paper, a stochastic finite element method (SFEM) is employed to investigate the probability of failure of cementitious buried sewer pipes subjected to combined effect of corrosion and stresses. A non-linear time-dependant model is used to determine the extent of concrete corrosion. Using the SFEM, the effects of different random variables, including loads, pipe material, and corrosion on the remaining safe life of the cementitious sewer pipes are explored. A numerical example is presented to demonstrate the merit of the proposed SFEM in evaluating the effects of the contributing parameters upon the probability of failure of cementitious sewer pipes. The developed SFEM offers many advantages over traditional probabilistic techniques since it does not use any empirical equations in order to determine failure of pipes. The results of the SFEM can help the concerning industry  to better plan their resources by providing accurate prediction for the remaining safe life of cementitious sewer pipes. Underground sewer pipes are required to resist and operate safely under various external loads, as well as severe environmental conditions. The degradation of sewer pipes over time in combination with the effects of overlaying soil and surface traffic loads can sometimes cause catastrophic failures in sewer pipes. Despite the ever increasing spending on prevention and mitigation, there are thousands of collapse reports per year in sewer pipe networks throughout the world. The consequences of collapses of sewers are socially, economically, and environmentally devastating, causing, e.g., enormous disruption of daily life, massive costs, widespread pollution, and so on. It is known that sewer collapses are predominantly caused by deterioration of the pipes. For cementitious sewer pipes, corrosion is the main cause of deterioration. Corrosion can cause reduction in structural strength of the pipeline, leading to pipe collapse. Severe localised corrosion can cause pitting; also resulting in the failure of sewer pipes ,2,3,4. Tversus their service life. Ahammed and Melchers )fP) is 10% . The service life of each FE model  can be evaluated using the results provided by the SFEM  then the service life of the sewer pipe is reduced from 60 years to zero years for the acceptable probability of failure of 10%. A similar trend can also be seen for other presumed acceptable values of probability of failure .After choosing the type of each parameter (deterministic or stochastic) and creating the FE models, the time-dependant SFEM were performed for different values of scaled parameters in order to study their effect on the probability of failure of concrete sewer pipes. the SFEM b. It canThe effect of the buried depth of the sewer pipe on the probability of failure is shown in i.e., h* and t*) and stochastic (F*) parameters on the probability of the failure of sewer pipes. In order to investigate the relative contribution and importance of each stochastic (random) variable in the probability of failure of concrete sewer pipes, a sensitivity analysis was carried out. The results of the sensitivity analyses for two examples with normalised soil cover (h*) after 100 years of service life are presented in i.e., α, λ) together contribute to nearly half (48%) of the probability of failure of sewer pipes. This shows the significant influence of corrosion in general and corrosion coefficients in particular on the prediction of probability of failure. In general, the results of the sensitivity analysis can be used to efficiently improve the design towards a higher reliability for sewer pipe projects or to enhance management, rehabilitation and spending on existing pipelines.i.e., corrosion and stress failure) were adopted to define the limit state functions. The results of the numerical simulations revealed a nonlinear relationship between most of the parameters and the probability of failure of sewer pipes. In addition the results of the sensitivity analyses showed the significant contribution of the corrosion parameters. Study of the available literature clearly demonstrated that there is a serious lack of monitoring data of underground sewer pipes. The monitoring field data compiled by water industry are neither readily available nor comprehensive enough to be utilised for appropriate analytical purposes. No doubt access to such data is of paramount importance to check the validity of developed model in this study. The authors are currently working with concerning industries in order to have access or compile the much-needed data. In the present study a stochastic finite element method was utilised to predict the probability of failure of concrete sewer pipes subjected to combined effects of corrosion and stresses. Uncertainties involved in pipe material, traffic load, and corrosion are considered to develop the stochastic finite element model. A nonlinear time-dependent model was chosen to predict the corrosion in concrete sewer pipes. The model parameters were chosen based on a set of existing data in the literature. A normalised numerical example was employed to investigate the effect of both deterministic and probabilistic parameters on the probability of failure of sewer pipes. Two mechanisms of failure (The results of the SFEM can be used to improve the performance and planning of existing sewer systems, by providing better predictions for the probability of failure of sewer pipes compared to the existing approaches. The SFEM can bring together the effects of contributing parameters in the probability of failure of the system being studied in a numerical framework with high precision. Using the SFEM, it is possible to study the effect of each parameter on the failure of the system and their interaction with each other. The SFEM also provides a time-dependant reliability analysis for predicting the remaining safe life of sewers, which provides a means to better manage the existing sewers and plan resources during their whole life of service.


In predisposed subjects with migraine or tension-type headache increasing intake of acute medications is associated with a progressive clinical worsening. When the days of symptomatic drug use reach a given threshold  and the headache has become chronic for at least three months, a causal relationship is deemed to exist between the medication overuse and the clinical worsening, and the headache is termed medication-overuse headache (MOH). MOH affects nearly 2% of the general population. It represents a highly disabling condition that impacts considerably on the quality of life of sufferers and on the society in general because of high levels of disability and use of healthcare resources.MOH is treatable: withdrawal from overused drugs leads to a clinically significant improvement in the majority of patients. Even more so, when it is performed within an integrated approach aimed at targeting frequent associated features/conditions  and in the most appropriate clinical settings . Some Authors also report improvement with prophylactic medication  alone.Increasing amount of evidence suggests that the clinical process leading to MOH is paralleled by the establishment of chronic sensitization, which is partly reversed by withdrawal of overused drugs. In addition, several experimental reports confirm that frequent use of analgesics or triptans facilitates nociception, probably via the overexpression of CGRP and neuronal NOS in the trigeminal ganglion.Clinical practice and analysis of the literature suggest that the beneficial effect of drug withdrawal tends to be more marked and abrupt as compared to the reported slower reduction of headache days when prophylactic medication alone is used. Direct comparison trials are however lacking.A major issue to be addressed is the high risk of relapse into overuse and pain chronicity following improvement. A good wealth of literature findings has allowed precise quantification of the rate of relapse into overuse and pain chronicity following drug withdrawal , while data are missing as regards relapse rates following prophylactic treatment alone for MOH.Patient's education regarding the need to stop overuse;Withdrawal from overused drugs;Management of comorbid conditions;Optimization of symptomatic medications;Personalization of prophylactic medication.Taking all these observations into consideration, and awaiting for the necessary evidence from comparative trials, presently the optimal approach to MOH seems to be provided by a multistep process that possibly includes all of the following procedures:


A substantial proportion  had primary physical illness, while 18%, n = 8606, had primary neurologic disorders. The commonest physical comorbidity was hypertension (4%) and diabetes (2%). A significant proportion of the populace with mental disorders appeared not to be accessing mental health care services, even when it is available. Meaningful efforts to improve access to mental health services in the northeast region of Nigeria will require successful integration of mental health into primary and general medical services.Mental and neurological disorders are common in the primary health care settings. The organization of mental health services focuses on a vertical approach. The northeast as other low income regions has weak mental health services with potentially huge mental health burden. The manner of presentations and utilization of these services by the population may assist in determining treatment gap. We investigated the pattern and geographical distribution of presentations with mental disorders and explored the linkages with primary care in northeastern Nigeria over the last decade. A retrospective review of hospital-based records of all the available mental health service units in the region was conducted over a decade spanning between January 2001 and December 2011. A total of 47, 664 patients attended available mental health facilities within the past decade in the northeast. Overwhelming majority (83%,  Mental, neurological, and substance use (MNS) disorders account for an estimated 14% of the global burden of disease . These dEvidence suggests that the burden of mental and neurological disorders predominates in the primary health care settings . Mental However, across the majority of low and middle income countries, a low level of skilled mental health professionals is the norm –7. This Available mental health care services are limited to a single tertiary mental health facility and psychiatric units in 5 general hospital settings in the entire northeastern region of Nigeria, comprising 6 states and serving a population of nearly 20 million people. Additionally, these mental health facilities also provide services to substantial parts of the neighbouring countries of Chad, Cameroon, and Niger republics.The life time prevalence of mental illness among Nigerians is 12.1% and the 12-month prevalence is 5.2%; and while 20% of these are severe enough to warrant hospital admission, only 8% of serious and debilitating mental illnesses are actually treated . In absoWhile the resources for mental health care services are clearly limited in northeast Nigeria, the burden of mental disorders is high and is comparable to what is observed in most low and middle countries . ParadoxAlthough the weakness of the mental health system of the region is evident and the needs for mental and neurological care services are high it is not known to what extent the available services are currently being utilized. It is also not known to what extent the needs for services remain unmet; the extent of communal utilization of the available mental health services is not known. This information is useful to provide useful insights and a basis for future regional mental health policy formulation, planning, or the implementation of national policies at the local regional level. It will also assist in achieving a nuanced understanding of the mental health gap of the region.This study therefore aimed at investigating the pattern and geographical distribution of presentation with mental disorders, along with an exploration of the linkages with primary care in northeastern Nigeria over the last decade.A retrospective review of hospital-based records of all the available mental health service units in the region was conducted over a decade spanning between January 2001 and December 2011.Study Setting. We studied the mental health services of the northeastern region of Nigeria comprising 6 states of Adamawa, Bauchi, Borno, Gombe, Taraba, and Yobe  were handled by the region's tertiary mental health facility. A substantial proportion  had primary physical illness, while 18%, n = 8606, had primary neurologic disorders. The commonest physical comorbidity was hypertension (4%) and diabetes (2%).The sociodemographics of the population of patients utilizing the mental health services in the northeast in the period under review in The overwhelming proportions of the patients were managed in Maiduguri, which is the solitary tertiary mental health facility in the region. The specialist hospital in Taraba saw the least number of patients over the last decade. See Primary neurological disorders were the most frequently seen conditions, followed by schizophrenia spectrum and depressive disorders, respectively. No personality disorders were diagnosed within this period. See Most of the disorders were handled by the tertiary mental health facility. Relatively few were seen at the mental health facilities in the general hospitals even though they are closer to the community.Primary physical health problems had a disproportionate representation in the out-patient clinic attendance, with 30% of the patients attending the out-patient clinics of the mental health facilities presenting with primarily physical health problems.Linkage of Mental Health with the Primary Health Care System. The linkage with the regional primary health care system was poor. Only one of the secondary mental health facilities had regular linkage networks and a referral system, with the tertiary mental health centre located in Maiduguri. There was no interaction or linkages between the secondary care and the primary care level.The total number of patients that utilized the facilities in the ten-year period falls short of the potential number of people in need of admission for a year only. This may be due to different factors at play preventing people from accessing the services being provided. These factors include lack of awareness , 15, stiAlthough psychosis constitutes low prevalence within the community , schizopOur study reveals the relatively higher burden on the tertiary health facility even though it is located in the regional capital which is geographically far from the majority of the region's population and a lower rate of utilization of the psychiatric units within general hospitals, which should be closer to the populace. This may be related to the poorly skilled manpower in these facilities or a lack of awareness that such services are available in the general hospitals.Headaches and the epilepsies (g40–g47) were seen in unusually large numbers. This may have been due to a massive public education campaign about the availability of services for this group of disorder through the electronic media over the last decade particularly the Federal Neuropsychiatry Hospital in Maiduguri, Borno state.It is also evident that very little has changed in terms of the policy recommendation of strengthening and integrating mental health into primary care in Nigeria, even though the country's mental health policy was passed over two decades ago (1991) as evidenced by the low levels of utilization of the psychiatric units located in the psychiatric units located outside the regional capital. It will appear that the pragmatic way forward to increase access to mental health care services in underserved populations such as the northeastern region of Nigeria will have to be based on the fulcrum of effective integration of mental health care services into primary and general medical care services. This will however require adequate training in mental health, as well as ongoing supportive supervision from the few available mental health professionals from the tertiary facility.Overall there is poor utilization of in-patient services by the population majority of whom were treated at the tertiary health centre. A significant proportion of the populace with mental disorders appeared not to be accessing mental health care services, even when it is available. Meaningful efforts to improve access to mental health services in the northeast region of Nigeria will require successful integration of mental health into primary and general medical services. Community awareness and mobilization to engage with and to utilize these services where available will also be pertinent.


Currently there is great interest in identifying critical residues in proteins, to improve our understanding and allow for the engineering of protein families. Diverse approaches combine sequence information, structural data, dynamics analysis and functional description to determine the importance of amino acids with regards to protein function. In this work, we propose a hybrid approach for the identification of critical residues in proteins, combining the use of evolutionary information (co-evolution), cross-correlation of atomic fluctuations derived from Anisotropic Normal Mode Analysis simulations  (ANMA) aBy combining the information of the covariance matrix derived from Statistical Coupling Analysis (SCA)  and the The hybrid approach ANMA.SCA opens a wide range of possibilities in the study of functional motion within protein families. By means of detecting networks of critical sites and their topology it is able to reveal the hidden aspects of protein dynamics.


To the editor: As members of the French Ministry of Health Working Group on autochthonous urinary schistosomiasis, we read with interest the 2 recently published articles regarding schistosomiasis screening of travelers to Corsica, France . In the study based on travelers from Italy (In the study by authors from the GeoSentinel Surveillance Network (Altogether, these 2 studies identified only 1 patient with parasitological evidence of infection that was attributable to the already known 2013 focus in Cavu River. Therefore, these articles do not provide evidence of transmission of schistosomiasis in Corsica after 2013 or outside the Cavu River.


Heart rate variability has been recognized as a parameter that partly describes autonomic nervous system modulation of cardiovascular system.Analysis of heart rate variability has been proposed as clinically important as predictive and monitoring factor in subjects with different cardiac disease conditions and in subjects who suffer from diabetes mellitus.Despite numerous clinical and experimental trials on the topic of heart rate variability in the setting of intensive care medicine there is a lack of appropriate technological facilites for routine monitoring and analysis of this phenomenon in everyday clinical practice.Assessment of the parameters of heart rate variability in critically ill patients with different disease condition.Recordings of forty-two consecutive patients with different disease conditions admitted to intensive care were included in the observational trial. Electrocardiogram was recorded in the periods after admission and primary stabilization of the general condition, and afterwards during the period of stay in intensive care every day (first week of stay). After recording, analysis of short-term segments of electrocardiograms was performed by means of software packages for heart rate vaiability analysis . Linear parameters in time domain  and parameters in frequency domain  and parameters of Poincaré plot  were analysed.Statistical analysis of the data obtained was performed by software package IBM SPSS version 20. Diversity of the clinical conditions of the patients and different medications that were used on regular bases limited statistical analysis to only descriptive statistics. Results of assessment of different parameters of heart rate variability in the setting of ICU, in small group of subjects with different comorbid states are presented in this paper.Subjects in critical state for different disease conditions or after trauma had different patterns of alterations of heart rate variability. In this small group of patients, despite considerable variations in reduction of different parameters of heart rate variability, alterations of heart rate variability were the most pronounced in subjects who had also had developed acute coronary syndrome before admission to the hospital.


Mus musculus), simian immunodeficiency virus (SIV) in rhesus macaques (Macaca mulatta) and human immunodeficiency virus (HIV) in humans.In this Opinion piece, I argue that the dynamics of viruses and the cellular immune response depend on the body size of the host. I use allometric scaling theory to interpret observed quantitative differences in the infection dynamics of lymphocytic choriomeningitis virus (LCMV) in mice  responses in the two host species. Asquith and McLean  during HIV and SIV infection can be used as a quantity for disease progression. The wide variation of this rate in HIV-infected humans, ranging from years to decades (Fraser et al., + T cell responses are slower in larger animals. Whether this influences the ability of the cellular immune responses to eradicate viruses during the acute phase of an infection remains unclear. Others have argued that the response rate of immune systems does not change systematically with body size. Instead, the sub-modular architecture of the immune system, where the number and size of lymph nodes increase sublinearly with body size, could balance the tradeoff between the local detection of pathogens and the global host response (Banerjee and Moses, In summary, there are indications that viral replication and the proliferation of CD8Discrepancies between experimental findings of the mice and human immune system have been described and illustrate that using mice as preclinical models for the study of human diseases can be challenging (Mestas and Hughes, The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area (VLPO) and the suprachiasmatic nucleus (SCN). We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages. The use of light for image-forming vision is critical in sighted animals as it is used to both detect and distinguish objects in the surrounding environment. In addition to its role in image-formation, light also exerts direct effects on physiology and behavior. These non-image forming processes include synchronization (entrainment) of circadian rhythms  has been shown to increase locomotor activity during the dark period  and melanopsin in mice has been shown to cause a switch to diurnal activity patterns in 80% of the animals (Doyle et al., The flip-flop switch model has been used extensively to highlight the control of behavioral state by the sleep and wake promoting systems. Briefly, the model proposes a mutual inhibition between the sleep and wake promoting systems which allow both rapid and stable transitions (Saper et al., The suggestion that light initiates a sequence of activation and/or inhibition across a range of regions during the induction of sleep has also been suggested to exist for the suppression of pineal function, phase shifting, corticosterone release, and core temperature decrease Morin, . The proIn this review, we discussed our current understanding of the neural circuits involved in the control of murine sleep by light at the level of the retina and the downstream brain areas. At the level of the retina, the rod, cone and melanopsin photoreceptors work together to drive a continuous light signal to the sleep promoting system in the brain Figures  and 2. HThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In addition, hb5 mutants exhibited aerial rosettes at the base of the lateral inflorescence branches instead of growing cauline leaves as in wild-type plants .The overall growth behavior of the mutants did not differ significantly from the controls, except the bolting and flowering time were altered in three of the mutant lines. Hypolignified The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Due to the intricate structure of porous rocks, relationships between porosity or saturation and petrophysical transport properties classically used for reservoir evaluation and recovery strategies are either very complex or nonexistent. Thus, the pore network model extracted from the natural porous media is emphasized as a breakthrough to predict the fluid transport properties in the complex micro pore structure. This paper presents a modified method of extracting the equivalent pore network model from the three-dimensional micro computed tomography images based on the maximum ball algorithm. The partition of pore and throat are improved to avoid tremendous memory usage when extracting the equivalent pore network model. The porosity calculated by the extracted pore network model agrees well with the original sandstone sample. Instead of the Poiseuille’s law used in the original work, the Lattice-Boltzmann method is employed to simulate the single- and two- phase flow in the extracted pore network. Good agreements are acquired on relative permeability saturation curves of the simulation against the experiment results. Accurate acquisition of the micro structure and flow properties of porous media is of great importance in petroleum engineering, biomedical science, micro-electronics, and composites  images based on the maximum ball algorithm  using 3D nineteen velocity model; In recent years, the Lattice-Boltzmann method (LBM) has been developed into an alternative and promising numerical scheme for the simulation of fluid flows and physics modeling in fluids. The scheme is particularly effective in fluid flow applications involving interfacial dynamics and complex boundaries   are assigned to study the effects on oil recovery. As is shown in Fig. This paper presents a modified method of extracting equivalent pore network model from the 3D micro-CT images based on the maximum ball algorithm. The improved partition methods are able to avoid tremendous memory usage when extracting the equivalent pore network model. Two types of micro sandstone images are used to display the pore network models and simulate for single- and two- phase flow. The porosity, calculated permeability of the pore network model agree well with experimental benchmark data of the original sandstone sample. Using the extracted pore network model and two-phase flow codes based on Lattice Boltzmann method, the simulation on water flooding mechanism is conducted to obtain the effects of wettability on oil recovery in the porous sandstone. Visualized water flooding process and the relative permeability saturation curves are obtained. Moreover, it is found that the optimal oil recovery would be realized in the mixed wettability reservoirs. Both of the two simulation results are identical to the experimental benchmark data, which verifies the feasibility of our pore network model and the simulation codes.However, the assumptions used in the pore network extraction algorithm, which leads to idealized shape, radius and connectivity of pore and throat, result in a lager porosity and permeability of the reconstructed model compared to the original sample. A further research focus on the reproduction of the pore structure for the real shape is worth of studying to realize a wider application in other fields.


Trauma is a well recognised risk factor for the future development of osteoarthritis (OA). The Armed Services Trauma and Rehabilitation outcome study (The ADVANCE study) is a 20 year cohort study comparing medical and psychosocial outcomes of military personnel both exposed and not exposed, to significant trauma.The Bio-Mil-OA study, a sub-study of the ADVANCE study, is an ideal opportunity to investigate the predictive value of biomarkers in joint pain and osteoarthritis.The ADVANCE study is a 20 year cohort study of 600 combat casualties and 600 matched non exposed participants investigating the predictive value of biomarkers and trauma on the long term development of pain and OA in the hip and knee. Validated serum biomarkers for OA, knee and hip radiographs and patient reported outcomes for pain and function will be taken at baseline and at 5 years.The predictive value of the biomarkers in predicting OA development and progression and joint pain in those exposed to different levels of trauma will be investigated using quantitative immunoassays for catabolic markers of cartilage matrix degradation.


The introduction of tooth colored resin composite had a significant impact in pushing dentistry into the esthetic arena based on 2 major developments: adhesion and light-cured materials. Different light curing devices were introduced based on the mode of action and wavelength properties. But probably one of the major breakthroughs of technology in clinical dentistry is the integration of laser therapy as a therapeutic option into treatment plan for clinical improvement. The introduction of different laser devices with different wavelengths  and biological interaction . Some papers on clinical studies encompass the effect of laser on the periodontium, effect of mouthwash on biofilm control, and the use of analgesic combination in the management of chronic temporomandibular disorders.We hope that the content of this special issue provides valuable insights on the interaction of oral tissues with lights and matters to clinicians and researchers.Samir NammourSamir NammourUmberto RomeoUmberto RomeoCarlos de Paula EduardoCarlos de Paula EduardoToni ZeinounToni Zeinoun


Lung cancer is the leading cause of cancer-related mortality in Canada  and arouWe have reached a plateau , 5 with Current recommendations for first-line treatment of advanced NSCLC use both histologic and molecular diagnostics in designing the course of treatment , 8. We hRecent advances in understanding signaling pathways for malignant cells, interconnections in those pathways, the importance of various receptors –15, and These treatments are aimed at specific  alterations in the malignant cells. Various NSCLC subtypes are associated with potentially targetable biomarkers such as mutation of the epidermal growth factor receptors (EGFR) –22, KRASKnowledge about the advantages of treatments with targeted agents in advanced NSCLC is rapidly growing, but the hope is to eventually apply this knowledge to earlier stages of NSCLC and thus to increase the cure rate of these patients. Combining various targeted agents or sequencing them properly will be of the utmost importance in the new era of personalized targeted therapy . Many clContributors in this issue of Frontiers in Thoracic Oncology describe the importance of team work  from diaOur review will cover the description starting with the interventional procedures , to treaWe hope to provide a complete review of present and future approaches to personalized medicine in advanced NSCLC, reflecting the present views, and practices in Canada.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Purkinje cells (PC) of the cerebellar cortex have two distinct firing signatures: simple and complex spikes. The simple spikes are due to the intrinsic mechanisms of the cell and synaptic inputs coming through the parallel fibers and molecular layer interneurons -3. The PIn this study we analyze how PC synchrony in the context of "pauses" in simple spikes affects different coding mechanisms of the neurons of the cerebellar nuclei. To this end, we use a computational model of a cerebellar nuclear neuron  and syntWe find that both the amount and type of pause synchrony is encoded as rate increases in the firing of the nuclear cell. Synchronized pauses briefly release the nuclear neuron from inhibition giving rise to well-timed spikes. Further, pauses synchronized with pause ending spikes caused greater firing rate modulation in the nuclear cell while pause beginning type synchrony enhanced the degree of timelocking. We also analyze the effect of pause length and spike jitter on the timelocking phenomenon of the nuclear neuron. We argue that these results lead to better understanding of how PC pause synchrony is processed in its target nuclear neuron.


Metapopulation processes are important determinants of epidemiological and evolutionary dynamics in host-pathogen systems, and are therefore central to explaining observed patterns of disease or genetic diversity. In particular, the spatial scale of interactions between pathogens and their hosts is of primary importance because migration rates of one species can affect both spatial and temporal heterogeneity of selection on the other. In this study we developed a stochastic and discrete time simulation model to specifically examine the joint effects of host and pathogen dispersal on the evolution of pathogen specialisation in a spatially explicit metapopulation. We consider a plant-pathogen system in which the host metapopulation is composed of two plant genotypes. The pathogen is dispersed by air-borne spores on the host metapopulation. The pathogen population is characterised by a single life-history trait under selection, the infection efficacy. We found that restricted host dispersal can lead to high amount of pathogen diversity and that the extent of pathogen specialisation varied according to the spatial scale of host-pathogen dispersal. We also discuss the role of population asynchrony in determining pathogen evolutionary outcomes. Relatively little is known about actual patterns of generalisation and specialisation in natural plant-pathogen systems largely because many fewer studies have focused on the pathogenicity structure of pathogen populations than on the resistance structure of their host populations. The spatial scale of interactions between a pathogen and its host is seen to be of prime importance in determining evolutionary trajectories of host-pathogen metapopulations because migration rates of one of the species affect the spatial and temporal heterogeneity of selection on the other. Here we develop a simulation model to specifically examine the joint effects of host and pathogen dispersal on the evolution of pathogen specialisation in a spatially explicit metapopulation. The present approach gives insights into the role of host and pathogen dispersal in driving pathogen diversity and adaptation and encourages further characterisation of the pathogenicity structure of crop and natural pathogen populations. In spatially structured populations, habitat spatial heterogeneity plays a crucial role in determining the potential for species and genotypes to coexist Some of the first models investigating the role of dispersal on host-pathogen coevolving patterns assumed a qualitative type of interaction (single locus population genetics model). The work of Gandon and colleagues et al. et al. et al.i.e. when hosts undergo disruptive selection and branch into two coexisting types. They found that branching was possible in a spatial model but requires higher virulence  and stronger trade-offs than in a non-spatial model . However, they did not characterise the coexisting genotypes. In contrast, in a similar model but focusing on pathogen evolution, Kamo et al.et al.Host-pathogen interactions are however not limited to qualitative relationships but are also largely determined by quantitative traits et al.Another crucial question that arises in coevolving systems is how the geographical structure of coevolution may shape spatial patterns of variation in the coevolving species Here we develop a simulation model to specifically examine the joint effects of host and pathogen dispersal on the evolution of pathogen specialisation in a spatially explicit metapopulation. We consider a plant-pathogen system in which the host metapopulation is composed of two plant genotypes and the pathogen is dispersed by air-borne spores. We assumed that the pathogen population is characterised by a single life-history trait under selection, the infection efficacy of the pathogen on the host genotypes. We did not consider environmental spatial heterogeneity. In particular we addressed the following questions: How do the scale of dispersal and the strength of evolutionary trade-offs affect the potential for multiple pathogen genotypes to coexist? Does the level of pathogen specialisation depend on host and pathogen dispersal scales? Is there spatial heterogeneity in patterns of diversity? We first present the model and the simulation experiment. Then we study the extent of synchrony among local populations, the effect of dispersal on pathogen diversity and level of specialisation. We also analyse the sensitivity of our results to the pathogen life-history traits, to the shape of the dispersal function and to the metapopulation structure. Finally we discuss our results with an emphasis on the role of population asynchrony in determining evolutionary outcomes.e.g. seeds and spores). The model describes a polycyclic disease caused by a foliar pathogen dispersed by air-borne spores (e.g. rust fungus). The model is stochastic and time is considered as discrete. In population We consider a metapopulation model in which plant and pathogen populations are inter-connected via dispersal of propagules  becomes infected with a probability Seeds and spores that fail to establish are removed (no seed or spore bank) which implicitly imposes a cost of dispersal. The different steps and their chronology are detailed in Appendix S1 in The host and pathogen metapopulation consists of a network of The probability that a spore (or respectively a seed) disperses from population The host population is composed of two resistant genotypes, The pathogen population is initially composed of one generalist genotype defined by a fixed infection efficacy on each host genotype. Specialist genotypes emerge through the balance of mutation and selection. They are defined according to the gain, in percentage of the infection efficacy of the generalist genotype, that they experience on the host to which they are adapted (their susceptible host) and the cost that they suffer on the other host (their resistant host). The gain of the generalist is by definition 0. We assume a trade-off between gain and cost such that the i.e. those with small gains or losses in Pathogen genotypes are classified according to their gain in infection efficacy on their susceptible host. Genotype 1 corresponds to the full specialist of host Ten mean dispersal distances (in proportion of the region size) were considered for both host and pathogen by varying We fixed the infection efficacy of the generalist to 0.2. In addition to the generalist we defined 10 specialists on each host  by increasing The probability that a spore was of the same genotype as its parental lesion was set as Sensitivity to the other parameters . Thus, boom and bust dynamics (time periods characterised by sustained increase in one of the host genotype followed by its sharp and rapid contraction in favour of the second host genotype) dominated the system . Thus, spatial coexistence was also observed  but the The mechanisms explaining the pattern of pathogen diversity when vs.When the trade-off shape was linear  was enhanced because of a reduce amplitude in oscillations and thus a reduce probability of fixation of one of the two full specialists  genetic cluster(s) with low genotypic variability (efficacy range). Here also among-population asynchrony was sufficient to allow spatial coexistence. As the scale of dispersal increased, the system became increasingly dominated by boom-and-bust dynamics. Local populations became increasingly synchronised and spatial coexistence was only transitory. For large pathogen and host dispersal scales, severe oscillations appeared leading to frequent local extinction-recolonisation of hosts. When moderately specialised genetic clusters were selected, these oscillations also resulted in the global extinction of one of the hosts and the subsequent full specialisation of the pathogen population on the remaining host. In this case the metapopulation acted as a single population where host and pathogen frequencies experienced growing oscillations, resulting in a single genotype of each species being fixed.et al.The effect of host and pathogen dispersal on the maintenance of diversity was specifically studied by Thrall and Burdon The competitive exclusion principle suggests that in an environment composed of two resources, competition can either lead to selection for a generalist or for two specialists. We found here that up to four pathogen genetic clusters can coexist in a two-resource (host) environment. Using a one-patch model for studying adaptive evolution, Abrams A particular feature of the current study was to characterise the level of specialisation, as measured by et al.The impact of gene flow on levels of pathogen specialisation has only rarely been discussed in the literature. Most studies deal with spatially unstructured populations et al.A contrasting pattern of specialisation was observed when pathogen dispersal was fixed to be spatially local  and host dispersal scale was varied. Under these conditions, the pathogen generally dispersed less than the host and it was expected that this differential would decrease the level of pathogen specialisation. However, contrary to this prediction, increasing host mean dispersal distance initially resulted in greater pathogen specialisation, which reached its maximum for intermediate host mean dispersal distances . For lare.g.et al.Puccinia triticina) on wheat (Triticum aestivum) at the scale of France and found coexistence among qualitative specialists (very restricted host range), quantitative specialists (large host range but transmitted efficiently only by a few of them) and generalists . This high diversity of pathogenicity patterns is consistent with the high diversity found here when the host disperses essentially locally. In addition, we found, in the present study, that more generalist, and thus less damaging, pathogen genotypes were favoured when the host population fluctuates in time because, under these conditions, the pathogen population is forced to track host oscillations. Such fluctuations in variety frequencies could be impose in agricultural landscapes to prevent the evolution of pathogen populations toward highly specialised and adapted morphs. Moreover, local spatial aggregates of crops or varieties that behave similarly with regard to a given disease should be avoided in order to prevent the local emergence of specialised (and damaging) pathogen genotypes.In our study, although the host population was diversified, we assumed that the properties of the two host genotypes did not change through time and thus that the pathogen evolves faster than the host. This is particularly the case for crops, for which the same host genotypes are used for several years and that integrate relatively low genetic diversity for disease resistance. In agricultural landscapes host dispersal and aggregation is restricted to spatial and temporal patterns of cropping. Although there have been a few attempts to produce advice on optimal crop spatial organisation for restricting pathogen evolution e.g., this quAnother example is provided by invasive plants which are likely to exhibit low diversity with respect to disease resistance Relatively little is known about actual patterns of generalisation and specialisation in natural systems largely because many fewer studies have focused on the pathogenicity structure of pathogen populations Text S1Model description and supplementary figures.(DOCX)Click here for additional data file.


Solanum lycopersicum) evolved from a wild ancestor (S. pimpinellifolium) bearing small and round edible fruit. Molecular genetic studies led to the identification of two genes selected for fruit weight: FW2.2 encoding a member of the Cell Number Regulator family; and FW3.2 encoding a P450 enzyme and the ortholog of KLUH. Four genes were identified that were selected for fruit shape: SUN encoding a member of the IQD family of calmodulin-binding proteins leading to fruit elongation; OVATE encoding a member of the OVATE family proteins involved in transcriptional repression leading to fruit elongation; LC encoding most likely the ortholog of WUSCHEL controlling meristem size and locule number; FAS encoding a member in the YABBY family controlling locule number leading to flat or oxheart shape. For this article, we will provide an overview of the putative function of the known genes, when during floral and fruit development they are hypothesized to act and their potential importance in regulating morphological diversity in other fruit and vegetable crops.Domestication of fruit and vegetables resulted in a huge diversity of shapes and sizes of the produce. Selections that took place over thousands of years of alleles that increased fruit weight and altered shape for specific culinary uses provide a wealth of resources to study the molecular bases of this diversity. Tomato ( Angiosperm plants vary tremendously in morphological traits related to their reproduction. The floral appearance is driven by evolutionary aspects of the pollination syndrome whereas distinct dispersal modes drive the evolution of phenotypes associated with the fruit. In natural settings, the main functions of the fruit are to protect the developing seeds and to act as a dispersal agent. The onset of the change to an agricultural lifestyle, approximately 10,000 years ago, provided strong selection pressures on the fruit of incipient vegetable and fruit crops. The selections made by early farmers offer a great opportunity to identify the molecular basis of a range of phenotypic traits, especially those related to fruit morphology and flavor. For example, selections against bitter taste resulted in palatable eggplant and cucumber  in promoters and coding regions underlie the phenotypic diversity of the tomato fruit.Even though the fruit is a terminal structure that forms relatively late in the plant's lifecycle, the formation of this organ and the parameters that determine its final dimensions are rooted much earlier in the plant's lifespan. Therefore, it is important to view tomato fruit development in the context of overall plant development starting after germination. Plant growth in tomato and other Solanaceous plants is characterized by a sympodial shoot architecture where after formation of 8–10 leaves, the shoot apical meristem (SAM) terminates into the inflorescence meristem (IM), and growth continues from lateral meristems called sympodial meristems (SYM). Meanwhile, the IM terminates into the floral meristem (FM) generating the flower  controls the number of carpel primordia and a mutation results in a fruit with more than the typical two to three locules   and a WD40 motif containing protein (Solyc02g083940). Further association mapping led to the identification of two single nucleotide polymorphisms located 1080 bp downstream of the putative tomato ortholog of WUS   leads to increases in locule number with more pronounced effects on locule number than lc  is considered to underlie fas  screens using Arabidopsis KNOX and BELL transcription factors as bait led to the identification of OFP members, lending support for the notion that OVATE interacts with patterning genes that impact fruit shape at the early stages of gynoecium development  . However, the most dramatic effect of SUN on shape is manifested after anthesis, during phase 5, which is the cell division stage of fruit development , Cucumis melo (melon) and Vitis vinifera (grape), the putative ortholog of KLUH and members of the same CYP78A class were associated with larger fruit, suggesting a possible role of this small and largely unknown cytochrome P450 family in parallel domestication processes in fruit and vegetable crops (Chakrabarti et al., CNR/FW2.2, members of the family regulate plant growth and biomass as well as ear length and kernel number per row in maize (Guo et al., FW2.2/CNR-like genes to control weight in a range of crop species (Paran and Van Der Knaap, The domestication of fruit and vegetable crops was likely driven by selections for increases in fruit weight and shape in many incipient crop species. Thus, the question arises whether any of the tomato genes or members of their families are associated with fruit weight and shape in other species. Of the fruit weight genes, other members of the CYP78A class to which WUSCHEL-like gene in soybean showed an enlarged gynoecium (Wong et al., WUS could impact the size of fruits and vegetables in other crops.Of the fruit elongation genes, down regulation of a member of the OFP family in pepper led to a longer shaped fruit (Tsaballa et al., ovate (Rodriguez et al., lc and fas mutants both provide evidence for the existence of other genes that interact with these major regulators of fruit shape and size. In addition, the identification of additional fruit weight QTLs (Huang and Van Der Knaap, Recent discoveries have started to shed light on the regulation of fruit shape and weight, and the molecular mechanisms underlying this diversity found in cultivated germplasms. However, these six genes are unlikely to represent the entire repertoire of genes acted on by domestication and diversification. The identification of suppressors of Advancing the research into the function of fruit morphology proteins is going to lead to fundamental insights into plant developmental processes. Especially processes that regulate cell proliferation and enlargement patterns, as well as its rate and duration are of particular importance since they pertain to growth of all plant organs and eventually yield. In all, the discoveries made using tomato fruit morphology as a model will undoubtedly support fundamental and applied research that is applicable to many other plant systems.All authors contributed critically to the writing and editing of the manuscript, agree to be accountable for the data presented and approve the version of the manuscript. Esther van der Knaap wrote the manuscript and constructed Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Migraine with (MA) and without aura (MO) is a common brain disorder that affects 15% of the general population. Genetic studies on twins have shown that MA and MO heritability spans between 50% and 60% and pharIn recent years the technologies for studying nucleic acids have literally exploded, opening to new possibilities for study of genetics and epigenetics of MA and MO.One of the most significant results is the sharp cost decrease for the whole genome DNA sequencing, since the psychological threshold of 1000$ for a 30X genome is about to be achieved. This cost reduction is fostering a wealth of large sequencing campaigns that will allow overcoming all the limitations due to the poor knowledge of human genetic variability that has plagued the ability of identifying the genetic basis of all sporadic diseases including MA and MO.The reduction of nucleic acids sequencing costs and the availability of cost effective microarray solutions for the analysis of DNA methylation has favored the implementation of epigenomic studies, in particular DNA methylation microarray has been thoroughly used providing new insight regarding the variability and the role of such epigenetic agent. DNA methylation, miRNA and histone modifications have proven to be a potential source of powerful and robust biomarkers.Taken together both the new genetic and epigenetic omic approaches have the potential to provide new molecular insight in the etiology of MA and MO. Moreover from such approaches we expect to obtain tools to improve migraine diagnosis, patient stratification, and therapy.None.


The activation of the classical renin–angiotensin aldosterone system (RAAS) is known to be involved in the regulation of blood volume and blood pressure and plays an important role in cardiovascular pathology including hypertension and heart failure. Evidence is now available that independently of the classical RAAS, several RAAS components are expressed in cells from different organs including the heart and kidney and are able to change important physiological properties like cell communication, heart excitability, and activation of ionic channels and cell volume when applied locally to the cells  or systeAlthough studies performed on transgenic animals generated controversial results, evidence is available that the overexpression of some components of RAAS like Ang II on cardiac muscle, elicit ventricular hypertrophy independently of changes in arterial blood pressure . FurtherThe harmful effects of Ang II on cardiovascular and renal systems inducing remodeling, seems, in part, related to increase in oxidative stress. The discovery of angiotensin converting enzyme 2 (ACE2)  and the In this Research Topic, the pathophysiological role of local RAAS in different tissues and organs are reviewed by different authors, each one expert in their respective fields –18. We hThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.