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Imaging the developing brain: what have we learned about cognitive development?
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1 Review TRENDS in Cognitive Sciences Vol.9 No.3 March 2005 Imaging the developing brain: what have we learned about cognitive development? B.J. Casey 1, Nim Tottenham 1, Conor Liston 1 and Sarah Durston 1,2 1 Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, 1300 York Avenue, Box 140, New York, NY 10021, USA 2 Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands The human brain undergoes significant changes in both its structural architecture and functional organization across the life span. Advances in neuroimaging techniques over the past decade have allowed us to track these changes safely in the human in vivo. We review the imaging literature on the neurobiology of cognitive development, focusing specifically on cognitive taskdependent changes observed in brain physiology and anatomy across childhood and adolescence. The findings suggest that cortical function becomes fine-tuned with development. Brain regions associated with more basic functions such as sensory and motor processes mature first, followed by association areas involved in top-down control of behavior. Introduction The year 2005 marks a decade since the first application of fmri to developmental questions [1]. It is well established that brain development and cognitive maturation occur concurrently during childhood and adolescence [2 4], but much less is known about the direct relationship between neural and cognitive development. This review highlights what we have learned about the biological substrates of cognitive development over the past decade, advances and limitations of the methods, and the relevance of these studies to understanding and developing interventions for individuals with atypical development. Emphasis is placed on studies that inform how cognitive development and learning map onto changes in brain anatomy, connectivity and physiology across childhood and adolescence. Contemporary non-invasive neuroimaging methods have provided developmental scientists with the opportunity to track safely cognitive and neural processes underlying human development (see Box 1). These methods have advanced the field of developmental neuroscience by providing evidence of changes in structural architecture and functional organization in the developing brain in vivo. However, these measures provide only an indirect measure of brain structure and Corresponding author: Casey, B.J. function. Changes in the volume of a structure or amount of activity as measured by MR methods lack the resolution to characterize the mechanism of change definitively. Histological evidence suggests that brain development is a dynamic process of regressive and progressive changes (see Box 2). As such, MRI-based cortical changes observed with development may be a combination of myelination, dendritic pruning and changes in the vascular, neuronal and glial density. Nonetheless, the methodologies provide information about regional development that, in conjunction with histological studies, could tease these processes apart. Furthermore, because these tools permit not only scanning of children but also repeated scanning of the same individual over time, they can provide measurement of general neuroanatomical changes with both learning and development. This review highlights MR-based measures of change in neuroanatomy, cortical connectivity and cortical function with learning and development. Neuroanatomical development of the human brain Several structural imaging studies have mapped the neuroanatomical course of human brain development [5]. The findings parallel many of the post-mortem histological findings, providing validity for in vivo imaging measures, and also parallel behavioral and cognitive development. Claims of causality between coincidental changes in brain and behavioral development is a common trap into which one could fall by simply assuming linear changes across systems and direct associations between these changes. Nonetheless, the synchrony in time course of the changes reported in MRI-based anatomical studies and cognitive development have driven more direct tests of these associations in functional imaging studies. For this reason, MRI-morphometric studies of change in structural architecture are highlighted. The most compelling reports of structural changes with development over the period of childhood and adolescence have come from recent longitudinal MRI studies [6,7]. In general, the sequence in which the cortex matures parallels cognitive milestones in human development [6 9]. First, regions subserving primary functions, such as motor and sensory systems, mature earliest, with /$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. doi: /j.tics
2 Review TRENDS in Cognitive Sciences Vol.9 No.3 March Box 1. Magnetic resonance methods Magnetic resonance technologies have introduced a new set of tools for capturing features of brain development in living, developing humans. The three most common MR methods used in the study of human development and learning are illustrated in Figure I. These imaging methods became especially important to cognitive and developmental scientists when the functional capabilities were discovered. The functional methodology measures changes in blood oxygenation in the brain that are assumed to reflect changes in neural activity [55,56], and eliminates the need for exogenous contrast agents, including radioactive isotopes [57,58]. DTI is a relatively new MR technique that can detect changes in white matter microstructure based on properties of diffusion [59,60]. Diffusion of water in white matter tracts is affected by myelin and the orientation and regularity of fibers and provides an index of brain connectivity. Because all three of these MR techniques are non-invasive, development and learning can be tracked more precisely within individuals with repeat scans over short or long intervals of time (days to years). Figure I. (a) Structural MRI produces structural images of the brain that are useful for anatomical and morphometric studies; (b) DTI measures connectivity of fiber tracts between anatomical structures; and (c) functional MRI measures patterns of brain activity within those structures. temporal and parietal association cortices associated with basic language skills and spatial attention maturing next. Higher-order association areas, such as the prefrontal and lateral temporal cortices, which integrate primary sensorimotor processes and modulate basic attention and language processes, seem to mature last [6,7]. Specifically, MRI-based measures showed that cortical gray matter loss occurred earliest in the primary sensorimotor areas Box 2. Structural architecture of the developing brain The human brain undergoes dramatic changes in both its structural architecture and functional organization that reflect a dynamic interplay of simultaneously occurring progressive and regressive events. Although the total brain size is about 90% of adult size by age 6 years, the brain continues to undergo dynamic changes throughout adolescence and well into young adulthood [61]. Figure I illustrates some of these developmental changes, including proliferation and migration of cells mostly during fetal development [62,63], regional changes in synaptic density during postnatal development [11,12,64], and protracted development of myelination well into adulthood [65]. Current non-invasive neuroimaging methods do not have the resolution to delineate which of these processes underlies observed developmental changes beyond gray and white matter subcomponents. Developmental course of human brain development Experience-dependent synapse formation and dendritic arborization Prefrontal cortex Parietal and temporal association cortex Sensorimotor cortex Neurulation Cell proliferation and migration Synaptogenesis and synaptic pruning Myelination Conception Months Months Years Birth TRENDS in Cognitive Sciences Figure I. See text for details. Adapted with permission from Ref. [66].
3 106 Review TRENDS in Cognitive Sciences Vol.9 No.3 March 2005 and latest in the dorsolateral prefrontal cortex [6,10]. These findings are consistent with non-human and human primate postmortem studies showing that the prefrontal cortex matures at a more protracted rate than sensorimotor cortex in synaptic density [11,12]. Cross-sectional studies of normative brain maturation during childhood and adolescence have shown somewhat similar patterns concluding that gray matter loss during this period reflects a sculpting process of the immature brain into the fully functioning mature one [10,13 16]. As such, the pattern of development observed is suggested to reflect the ongoing neuronal regressive events, such as pruning and the elimination of connections. Developmental changes in subcortical regions occur over this period of development as well [10,13,15 19]. One of the more reliable patterns reported is in subcortical regions to which association cortex projects. For example, both cross-sectional [19] and longitudinal studies [6] show patterns of development in portions of the basal ganglia to which the prefrontal cortex directly projects. Again, this pattern could reflect the gradual elimination of connections, with strengthening of others. What is the corresponding pattern of change in white matter volume over this period? In contrast to an inverted U-shaped pattern of development in gray matter with age, white matter volume increases in a roughly linear pattern, increasing throughout development until approximately young adulthood [6,13,14,17,20], as evidenced by increases in volume and density [17]. These changes presumably reflect ongoing myelination of axons by oligodendrocytes enhancing neuronal conduction and communication. Therefore, both regressive and progressive processes are occurring in parallel, which could enhance neural and cognitive processes. Connections are being fine-tuned with the elimination of an overabundance of synapses and strengthening of relevant connections with development and experience. How do these structural changes relate to cognitive changes? Developmental changes in cortical development have been found to correlate with behavioral performance measures. Sowell and colleagues [4] showed an association between prefrontal lobe structural maturation and memory function using neuropsychological measures. Similar associations have been reported between MRI-based prefrontal volume and specific measures of cognitive control (i.e. the ability to override an inappropriate response in favor of another) in cross-sectional studies [21,22]. Together these studies suggest that, perhaps not surprisingly, functional changes in brain development are reflected in structural changes. Development of human brain connectivity The MRI-based morphometry studies reviewed suggest that cortical connections are being fine-tuned with the elimination of an overabundance of synapses and the strengthening of relevant connections with development and experience. Recent advances in MR technology, such as diffusion tensor imaging (DTI), provide a potential tool for examining the role of cortical connectivity in the development of cognitive and brain development in greater detail. This method (see Box 1) provides information on directionality and regularity of myelinated fiber tracts (e.g. [23]). Until recently, few studies have linked brain connectivity measures with cognitive development, although indirect measures of white matter suggest regional development in prefrontal cortex and presumably in function [23]. Of these studies, one showed that development of working memory capacity was correlated positively with prefrontal parietal connectivity [24], consistent with imaging studies showing differential recruitment of these regions in children relative to adults [39,42]. Using a similar approach, Liston and colleagues [25] showed that DTI-based connectivity in both frontostriatal and posterior fiber tracts correlated with age, but only frontostriatal connectivity correlated with efficient (fast and accurate) performance on a Go/No-go task. The prefrontal fiber tracts examined were defined by regions of interest identified in an fmri study using the same task [42]. Similarly, combined DTI and fmri analytical approaches have shown the importance of the maturation of prefrontal parietal connectivity in the performance of a working memory task [26]. As such, DTI and fmri-based measures with these regions correlated across age. In these studies, measures of brain connectivity were correlated with development, but specificity of the involvement of particular fiber tracts in cognitive performance was shown by dissociating the particular tract [25] or cognitive ability [24]. These dissociations are important when distinguishing between performance and agerelated differences in imaging measures. Functional organization of the developing human brain What do the previously described changes in brain structure, such as prolonged development of the prefrontal volume and connectivity, mean in terms of function? The development of the prefrontal cortex is thought to play an important role in the maturation of higher cognitive abilities [27,28]. Mature cognition is characterized by the ability to filter and suppress irrelevant information and actions (sensorimotor processes), in favor of relevant ones (i.e. cognitive control) [27]. A child s capacity to filter information and suppress inappropriate actions in favor of appropriate ones continues to develop across the first two decades of life, with susceptibility to interference from competing sources lessening with maturity [29 32]. Many paradigms used to study cognitive development require cognitive control such as the Stroop and Go/No-go tasks [33 35]. Collectively, imaging studies using these tasks as probes show that children recruit distinct but often more prefrontal regions, both ventral and dorsal, when performing these tasks than do adults. Based on cross-sectional [36] and longitudinal studies [37], regions whose brain activity correlates with task performance (reaction time and/or accuracy) become more focal or fine-tuned, whereas regions not correlated with task performance decrease in activity with age (see Figure 1). It has been suggested that this pattern of activity, observed across a variety of paradigms, reflects development within, and refinement of, projections to and from these regions [28,30,34,36,38], consistent with the DTI findings presented previously.
4 Review TRENDS in Cognitive Sciences Vol.9 No.3 March Figure 1. The development of human cortical function, as measured by contemporary imaging methods, reflects fine-tuning of a diffuse network of neuroanatomical regions [28,36,37]. Collectively, developmental neuroimaging studies of cognitive control processes suggest a general pattern of increased recruitment of slow maturing prefrontal cortex (references depicted here in red), especially dorsolateral prefrontal cortex [30,35,36,40,43] and ventral prefrontal cortex [28,34,37,39,42], and decreased recruitment of lower level sensory regions (references in blue), including extrastriate [36,40] and fusiform cortex [40] and also posterior parietal areas [30,37,38]. Importantly, specific activations vary with task demands, so working memory [43] and Stroop tasks [35] recruit different regions from response inhibition tasks [28,34,37,39,41,42]. This pattern of activity, which has been observed across a variety of paradigms, suggests that higher cognitive abilities supported by association cortex become more focal or fine-tuned with development, whereas other regions not specifically correlated with that specific cognitive ability become attenuated. AZanterior; PZposterior. Performance differences versus maturational differences The region-specific differences in activation with age that have been reported could reflect maturation, but might also reflect simple performance differences. For this reason, the collection of behavioral responses is crucial across these studies. As children almost always perform worse than adults on higher cognitive tasks, without equating performance between age groups or controlling for performance differences it is difficult to specify whether the activation differences are age related or simply reflect an overall difference in performance. To address this issue, investigators have adopted different approaches for teasing apart age versus performancedriven differences. One key strategy is to use performance matching to equate behavioral performance [28,36,39,40]. Post hoc, subjects are divided into subgroups based on behavioral performance that is either matched across groups or not matched [40]. Three patterns of activation emerge from performance matching-based analyses: (i) performance/age-independent; (ii) performance-related; and (iii) age-related. These patterns help to identify the basis of the observed activation and/or regional differences and how they relate to the task demands. As such, this approach provides a better understanding of how maturation relates to increased cognitive abilities. For instance, in a study of cognitive control that showed performance-related neural recruitment [39], children were divided into better and worse performers. Children with effective response inhibition did not recruit the same prefrontal regions as those activated by adults, suggesting an age-related recruitment in this region. However, they did recruit a subset of the same posterior association areas (parietal regions) consistently activated in adults. Children with poor response inhibition did not recruit these posterior regions, suggesting that improved ability to withhold an inappropriate response might first require mature activation of posterior parietal regions that is task specific. Tasks of lesser cognitive demand (e.g. selective attention tasks without response competition) do not seem to show age-related differences [41]. As not all tasks yield comparable performance across age groups, a second approach that has been used to equate performance across groups is to manipulate task difficulty parametrically (e.g. [42,43]). In a parametric design, task difficulty is varied with increases in task demands (e.g. increased response competition, memory load or stimulus degradation), allowing comparisons between children and adults on trials equated for accuracy. Durston and colleagues [42] used a version of a Go/No-go task that parametrically manipulated the number of Go trials (responses) preceding a No-go trial (withhold response). Behaviorally, they showed that both children and adults had more errors as the number of responses preceding a No-go trial increased. Children, however, had as many errors for No-go trials following a single Go trial as adults had when a No-go trial followed as many as five Go trials. The imaging data from adults showed a monotonic increase in association areas of the ventral prefrontal and posterior parietal cortices as the number of Go trials preceding a No-go trial increased, but children activated these regions maximally regardless of whether they had to withhold a response after one, three or five Go trials (responses). These data are consistent with other reports showing [39] that immature cognition is characterized by an enhanced sensitivity to interference from competing sources (e.g. response competition) that coincides with immature association cortex, specifically in prefrontal and posterior parietal-related circuitry. Cross-sectional studies versus longitudinal studies Most of the developmental observations described above have relied on cross-sectional samples (e.g. [36]) or even comparisons across studies [1,44].However,cross-sectional analyses might falsely suggest changes over time or fail to detect the specificity or magnitude of these changes, given the large individual variability in brain structure among individuals, especially during development [6,7,15]. In a recent study, Durston and colleagues [37] used fmri to track cognitive and brain development from late
5 108 Review TRENDS in Cognitive Sciences Vol.9 No.3 March 2005 childhood into early adolescence during performance of a Go/No-go task. There was a developmental shift in patterns of cortical activation from diffuse to focal activity similar to those reported in large cross-sectional studies [36]. Regions uncorrelated with task performance were recruited less with age, whereas a region in the ventral prefrontal cortex that correlated with performance (speed and accuracy) in this study and prior studies [28,42,45,46] showed enhanced recruitment. This change in pattern of activity was associated with enhanced performance of the cognitive control task. Activation in earlier developing regions such as the primary motor cortex remained unchanged. A parallel cross-sectional analysis based on a second group of children, the same ages as the longitudinal group, showed less specific results, supporting the importance of longitudinal studies in evaluating cortical changes with age. These studies, together with the longitudinal MRIbased morphometry studies [6], suggest differential developmental trajectories for sensorimotor relative to association areas such as the prefrontal cortex. Both the imaging-based neuroanatomical studies and the functional studies highlight the importance of examining changes in ability within individuals over time. As such, this work can begin to delineate processes specific to learning or development. Cortical organization with learning The importance of tracking cortical changes in individuals over time is perhaps most evident in the area of learning. Using repeated scanning of the same individuals, Karni and others (e.g. [47,48]) have shown rapid learning effects in primary motor cortex of adults during motor sequence learning that were apparent within a single imaging session, but that increased over weeks of training. This use of fmri to trace learning-related changes in cortical areas is currently being used by others in adults (e.g. [49,50]). Across these studies, the pattern of results shows that activity in task-relevant regions becomes increasingly enhanced with training, whereas task-irrelevant regions become less activated over time [50]. This pattern of change during adult learning studies mimics the observed changes in cross-sectional [36] and longitudinal [37] developmental studies. The findings highlight the importance of examining and distinguishing between contributions from experience and learning compared to those associated more with maturational development, in driving the cortical patterns of activation observed. Future directions Future research will no doubt take advantage of the ability to image children multiple times with fmri over the course of learning to delineate developmental and experience-based processes in cortical activity (see Box 3). For example, to determine whether the immature brain after extended practice engages in the same neural processes as the mature brain, we could compare brain activity in the mature system with brain activity in the immature system both before and after extended experience. Investigators are already beginning to take advantage of this approach in investigating the impact of Box 3. Questions for future research Do the biological substrates of learning and development differ? On what timescale can we see neuroanatomical and physiological changes with learning and development? What neural changes coincide with enhanced learning during development that could hinder learning with maturity? How can we move beyond claims of causality between coincidental changes in brain and behavioral development with converging methods? Can typical human development provide important clues on the type and timing of interventions with atypical development? behavioral and cognitive interventions on developmental disorders such as dyslexia [51,52] and attention deficit hyperactivity disorder [53]. Another future direction of developmental imaging studies will be in the combined use of complementary imaging methods. For example, a method not mentioned in this review, but one that has been used to address questions about cognitive and brain development, is electrophysiology. This technique records brain electrical activity that can be time-locked to presentation of a stimulus or to the production of a response (i.e. eventrelated potentials or ERPs). These electrophysiological measures have millisecond temporal resolution that can provide important information on the developmental changes in the temporal characteristics of neural and cognitive processes beyond that provided by fmri [54]. Clearly, the combination of these two techniques, together with other methods such as DTI, will strongly enhance our ability to understand neural and cognitive development and constrain current developmental theories. Investigators have begun to move in that direction with parallel fmri and DTI studies in adults and children [25,26]. Conclusions Findings from both cross-sectional and longitudinal imaging studies of late childhood and adolescence show that brain regions associated with more basic functions such as motor and sensory processes mature first, followed by association areas involved in top-down control of thoughts and action. This pattern of development is paralleled by a shift from diffuse to more focal recruitment of cortical regions with learning and cognitive development. Fine-tuning of cortical systems occurs with protracted refinement of association cortex (e.g. prefrontal cortex) relative to sensorimotor cortex. These findings seem to parallel changes observed over shorter time periods in studies of adult learning. The reported shift in cortical architecture and function is presumably an experience-driven maturational process that reflects fine-tuning of neural systems with experience and development, but future work delineating how learning during development affects this pattern is needed. These imaging studies map onto findings from animal and human postmortem studies indicating that pruning and elimination of connections, in combination with strengthening of relevant ones, occur during this time period, and illustrate the subtle interplay between neuroanatomical and physiological changes in neural circuitry and cognitive maturation.
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Explore MDVIP Member Reviews
Mar 28, 2017
I have been a patient of Dr. Blomgren's for more than 30 years and honestly don't know where I would turn for good, knowledgeable, reliable and friendly medical advice. He has helped me through many health issues. I trust any suggestions and advice he gives me without question. He is a great diagnostician, but if he doesn't know the answers he doesn't hesitate to refer me to someone else with a specialty in that field. I respect him in all aspects of my care. He is a friend as well as my doctor.
Mar 24, 2017
Dr. Blomgren is an excellent doctor. He listens to his patients, and he is very thorough in his explanations. My previous doctor simply would not listen to me. Dr. Blomgren is generous with his time and will call to follow up. He truly cares about his patients, and he treats them as if they are fellow human beings rather than their diseases or conditions. He takes an interest in their lives. He had been my doctor before he joined MDVIP, but I had to leave his practice because of insurance. I was very happy that Medicare allowed me to come back.
Feb 19, 2015
I have been a patient of Dr. Blomgren's for over 30 years. I respect his professionalism and knowledge. I look to him for all of my medical advice and know that he has my best interest at heart. He is my friend as well.
Feb 20, 2014
Dr. Blomgren is a great doctor! I feel like he truly cares about his patients. He is always available and will give you all the time you need to go over your issues. He is a caring and understanding doctor. I have never felt rushed at an appointment. I feel that he has patients ' best interest at heart and I think his dedication shows it. He will make suggestions to his patients on how to improve their health and be proactive about their health.
Feb 16, 2014
Dr. Blomgren is one of those Doctors (very few these days) that actually listens to what you are saying. Just carrying on a general conversation he listens and then puts it together with your exam. During one of my check-ups I had been having all kinds of weird things happening and by the end of the exam he was making an appointment with a cardiologist. I not sure another doctor would have reacted so quickly. He really cares!!
Feb 15, 2014
I've had an absolutely positive experience with my medical care from Dr. Blomgren since he inherited me from his retiring associate Dr. Keller. By the time of my first appointment, he had studied my file so thoroughly that he knew as much about me as I knew about myself. His Johnny Carson sense of humor matches perfectly with my sardonic wit. We communicate well, and, since I've reached the age of 60, he encourages me to take an active part in my wellness program. His proactive emphasis on wellness and prevention - rather than just waiting for something to happen and then finding a cure - reveals that he is truly interested in the welfare of his patients.
Feb 11, 2014
Dr. Blomgren has always been a thorough and sensitive caring doctor. MDVIP did not change that. It just gave him more time to be even more thorough and comprehensive in his exams. He has been my doctor since I was about 20 years old. And making fun of me when I had inner ear problem because he knew I could not and still cannot swim, is just an example of how he makes his office visits as easy and as comfortable as possible. I have grown to think of his as a friend and not just my general physician. I thank you for always pushing me to take better care of myself and for understanding when life is kicking me in the backside and I just can't seem to take my daily vitamin D and calcium, for calling in prescriptions when I am out of town and need help and for always calling me back. Thank you and I pray you will continue to have a wonderful career and practice.
Feb 11, 2014
Dr. Blomgren has been my primary care physician for approximately 34 years. We have a good understanding of what a good doctor-patient relationship is. When I have a need to see him the wait is short and I can rely on a professional and knowledgeable response. He is so thorough in diagnosing my symptoms and I just know I am in good hands. I have been preparing to travel and he has helped me locate a doctor in the area where I will be staying so should I need medical assistance it is easy enough for me to find. Thank you Dr. Blomgren for taking such an interest in me and the rest of your patients. I appreciate you.
Feb 9, 2014
Dr. Blomgren has been my doctor for over 30 years. He has detected problems when no one else could and I know that he has saved my life and is still doing that. He detected my first heart attack and sent me straight to the hospital. He listens and understands when you confide in him and makes things seem better. He has time to talk with you and to help you with any problems. His office staff is great and you know that your message will get to him in a timely manner, which is also very important.
Feb 7, 2014
Dr. Blomgren has consistently provided proactive health care for me. I have know him for over 30 years and have a lot to be thankful to him for. Just for starters, he detected a cancer early and probably saved my life! Not much to say after that except that I think he is a great doctor and I will always be appreciative for the care that he has given me. You are the best Peter!
Feb 7, 2014
Dr. Blomgren and his staff Cheri and Christie, have made a hugh impact on our lives! Dr Blomgren has met us after hours, calls us with follow ups, always is pleasant, AVAILABLE, and very thorough! He has seen our Son without hesitation when we would have to spend hours or days to see someone. Any time we call we get a happy professional voice with an attitude of willingness to help. The personal attention and the attention to the details of our health is well worth the membership fee!
Feb 6, 2014
Since I was adopted at 6 months of age, there is a great deal that we do not know about Family inherited ailments and disease. Dr. Blomgren has been able to guide me through this obstacle, identify potential conditions and carefully arrange a course of treatment specific to my personal needs. His attention to detail and his willingness to communicate with me at all times of the day or night is invaluable. The peace of mind I enjoy - having Dr. Blomgren as my MDVIP Physician is unmeasurable.

subset: commoncrawl


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North Judson-San Pierre Middle School is holding their 6th annual Walk for Wellness on September 23rd.
The walk and other activities are on Friday, September 23rd and all students will participate in the educational part of the day. Raising $10 allows the student to participate in the walk-a-thon on our track. $15 allows the student to take part in other fun activities provided by each grade level team. Past activities have included swimming, minute to win it, and an obstacle course.
Last year, they raised a total of $6,370. If the students raise over $8,000 this year, several willing staff members will take a pie in the face from select students. If the students raise $10,000, Principal Kelly Shepherd has agreed to let the students shave his head with clippers. The event itself consists of various activities for the students to partake in depending on how much money the student raises. All proceeds go towards the fitness center.


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Professionals must be registered so you can be sure:
What is a protected title?
Each profession we regulate has at least one protected title such as 'chiropodist' or 'physiotherapist'. Anyone who practises in the UK using one of these protected titles must be registered with us or we will take legal action against them.
What is registration?
Being registered with the HCPC means that a professional meets national standards and they are practising legally, safely and effectively, and they are entitled to use a protected title.
How does the HCPC monitor standards?
We investigate concerns raised about professions and can take action against those that do not meet our standards. We also approve the training and education programmes which entitle professionals to apply for registration with us. Once registered all professionals must undertake continuing professional development to keep their skills and knowledge up to date.


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2 x Metal Ground Spikes
1 x Oxford Carrying Bag with Zipper
11ft Teardrop Flying Banner with Ground Spike - 2PCS
Availability: In Stock
Buy 2 with 2% discount each
Buy 5 with 5% discount each
Buy 10 with 10% discount each
Features & Benefits:
Full color printed banner with custom design image, making perfect advertising effect.
Aluminum and fiberglass flag pole are lightweight & portable.
Double see through fabric for single-sided graphic.
100% polyester fabric for double-sided to ensure your message can be seen from either side.
Flag with metal ground spike: sturdy & weather resistant & durable.
Great for indoor & outdoor advertisement, trade show exhibits, events, special promotion, fairs etc.
Direct manufacturer & short turnaround time.
Lower shipping cost and fast delivery.
No MOQ.
Packaging & Delivery:
Packaging Details: Oxford Carrying Bag & Outer Carton.
Delivery Time: 3-5 working days.
Display Size: H335 cm
Graphic Size: W120 x H280 cm
Packing Size: W22 x H11 x L121 cm
We extend a full range of shipping methods to meet your budget and your deadlines.
UPS Surface Mail**
Around 7 working days***
DHL Express Mail
Around 3 working days
Data taken from
*These shipping speeds are estimates only. Delivery time will depend upon a combination of factors including the time the order was placed, the shipping method specified and the destination of the order.
**Applicable to UNITED STATES OF AMERICA only.
***Working days include from Monday to Friday, excluding holidays.
One year warranty is available on hardware. FREE Accessories Offering once ordered our items.
Please contact us whenever issues occur and we would try our best to assist.
Here are some information you may be interested in. For more details, feel free to contact our sales.
Q1. Can the size of the display be customized?
A: YES. We have our own factory and technical team, most of the product's size can be customized. Any size wanted, please tell us and suggestion will be provided by our professional workers.
Q2. Are the banners colorfast?
A: Banners cannot be colorfast for lifetime, and it's affected by many factors, such as local climate, site, frequency etc. You can tell us about the conditions to get the reference time.
Q3. Are the banners and hardware recyclable?
A: Both of the banner and hardware are recyclable. Banners are printed by dye sublimation, washable without fading. And it's easy to change the banners for the display stand.
Q4. Can you help with my design?
A: If you want us to make you the design, please send us original pictures & words in document and describe your promotion aims in details. Design charge will be USD 50.00 - 80.00/pc. The artwork should be in JPG, PDF, PSD, AI, EPS, TIFF, CDR format; CMYK ONLY, at least 70dpi.
Q5. What is your lead time/turnaround time?
A: This is mostly depending on the order's quantity and the product's stock. Time for Reference is as follow:
*50pcs hardware ONLY: 2-3 working days;
*50sets both hardware & banner: 5-7 working days;
*sample: 2-3 working days upon confirmation of e-proofs.
Q6. Which way do you ship?
A: Shipping by express, by air & by sea depends on demand. Worldwide shipping services are available.
Q7. How long is the warranty of your product?
A: One year warranty on hardware. FREE Accessories Offering once ordered our items. Please contact us whenever issues occur and we would try our best to assist.
Q8. Can I return the product if I am dissatisfied with them?
A: Sure. But All items must be returned in their original status & package within 7days. ONLY stand returning acceptable, as image made accordingly and could not resell. Buyer takes care of ALL return fees. And Original Shipping & Handling Cost would NOT be refunded.
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Save Big On Open-Box & Used Products: Buy "Nespresso Pixie Espresso Maker, Electric Titan (Di..." from Amazon Open-Box & Used and save 50% off the $229.00 list price. Product is eligible for Amazon's 30-day returns policy and Prime or FREE Shipping. See all offers from Amazon Open-Box & Used.
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Nespresso Pixie Espresso Maker, Electric Titan (Discontinued Model)
|$172.99 & FREE Shipping. Details
- Enter your model number to make sure this fits.
- Easy insertion and ejection of capsules. Compact Brewing Unit Technology
- Thermoblock heating element - Fast preheating time: 30 seconds
- Folding drip tray accommodates tall recipe glasses - Automatic and programmable coffee volume quantity
- Backlit LED water level detection indicators
- Holds 10 used capsules. Removable water tank: 24 oz or 0.7 L, 1 year warranty from date of purchase and registration
- Programmable buttons for espresso and lungo, folding drip tray for larger cups and recipes, brew ready in 25-30 seconds
- Backlight indicators, water level detection, auto power-off, used capsule container, convenient power cord storage
Frequently bought together
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Special offers and product promotions
From the manufacturer
Compact design
Thanks to its compact dimensions, the Pixie coffee maker fits in any kitchen and is available in a wide range of colors and 2 finishes. Only 4.3 inches wide, it uses hardly any space and is perfect for smaller urban kitchens.
Espresso and Lungo
The one-touch buttons with two cup capacities (Espresso and Lungo) can be reprogrammed to custom volumes and are backlit for ease of use. The folding drip tray accommodates differing cup sizes for espresso and milk coffee lovers alike.
High pressure pump
The 19 bar high-pressure pump allows for a barista-style result, unlocking the delicate flavor and premium aromas of each coffee capsule during the brewing process and creating an incomparably dense and unctuous crema. The fast heat-up system reaches the ideal temperature in just 25 seconds.
Empty water tank alert
Red backlights along the sides of the machine light up to alert you when you need to refill the water tank. With the automatic power-off function, the machine turns off 9 minutes after the last use, consuming less energy.
Instant enjoyment
Each machine includes a welcome set with 16 capsules containing individual aromas. Try each Grand Cru to find your favorites.
Nespresso capsule system
The Nespresso capsule system delivers exceptional taste and unique aromas thanks to the preparation of high-quality coffees in hermetically sealed and recyclable aluminium capsules for coffee enjoyment at the highest level.
The Nespresso Club
Order your Nespresso capsules through the Nespresso Club; online, by telephone (24 hours a day, 7 days a week) or in one of our Boutiques. Receive personalized advice and obtain technical support for your machine: whatever you are seeking, the Nespresso Club is with you every step of the way.
We also offer a capsule recycling service to all Club Members in the United States.
The Positive Cup
We believe that each cup of Nespresso has the potential to not only deliver a moment of pleasure but also restore, replenish and revive environmental and human resources. In effect, a cup of coffee that can create a greater value for society and the environment.
This is the Positive Cup vision and continues Nespresso's commitment to sustainability in coffee sourcing and consumption.
Technical specifications:
- Dimensions (WxHxD): 4.4 x 9.3 x 12.8 in
- Water Tank Capacity: 24 oz
- Container capacity: 9-11 used capsules
- Weight: 2.8 kg
- Dimensions of the box (WxHxD): 7.5 x 12 x 14.4 in
- Power: 120 V
- Pump Pressure: 19 bar
- Cable length: 2.6 ft
- Cup Warmer: No
- Removable Water Tank: Yes
- Filter included: No
- Power Save mode Yes
Nespresso Pixie
The Nespresso Pixie coffee machine offers avant-garde design with elegance and functionality. Equipped with a wide range of advanced features, the Pixie machine is energy efficient with a surprisingly compact design.
Streamlined for maximum efficiency, this coffee maker lives up to Nespresso's reputation for high-end technology. Each machine includes a welcome set with 16 Nespresso capsules containing individual aromas.
Box contents:
- Nespresso Pixie machine
- Welcome pack containing 16 Nespresso Grands Crus capsules
- Instruction booklet
- Information folder
|Pump pressure
|19 bar
|19 bar
|19 bar
|Empty water tank detection
|Fast 25" heat-up
|Programmable, one-touch buttons
|Espresso & Lungo
|Espresso & Lungo
|Espresso & Lungo
|Movable drip tray for large cups
|Foldable drip tray
|Foldable drip tray
|Foldable drip tray
|Energy consumption class
|Automatic power off
|Water tank capacity
|24 oz
|24 oz
|34 oz
|Dimensions (WxHxD)
|4.7 x 9 x 12.6 in
|4.4 x 9.3 x 12.8 in
|5.1 x 10.9 x 14.6 in
|Special features
|Lightest machine - Wide range of fashionable colors
|Avant-garde design - Compact size - Premium aluminium siding
|Retro-modern design
Product description
Nespresso Pixie C60-US-TI-NE, Electric Titan -the pixie heats up in only 25-30-seconds.
Customer reviews
Top customer reviews
So far, I love this machine! It's sleek and small so it doesn't take up much space. It brews quickly and isn't too loud. I'm still deciding what "flavor" of pod I like the best. I'm a fan of the dark, syrupy ones so far.
I'm glad I bought the Pixie instead of the Inissia although I'm sure that machine is well made, too. It just depends on what you want and whether you're the type of person who will eventually upgrade. I am, so I figured I'd do it sooner rather than later.
Nespresso currently has 5 different machines to choose from, however the most affordable are (in order): the Inissia ($149 list, $99 on Amazon), the Pixie ($229 list, $158 on Amazon) and the CitiZ ($299 list, $175 on Amazon). There is very little difference between these machines in terms of the guts of the machine. They all offer the 19 bar pressure, have a handle that opens the top for the pod insertion, built-in water containers of roughly the same size, and programmed buttons for the amount of espresso you wish to brew. These can be reprogrammed to suit your personal preference on all these machines. The machines mentioned can be bundled with a separate milk frother/heater for about $50, and they come in a variety of colors. The less expensive models, like the Inissia and the Pixie, have more plastic parts in them than the more expensive machines, with the idea of offering the Nespresso system to newcomers who wish to keep their initial outlay lower, but they all basically make the same cup of coffee.
The Pixie is the in the middle of the affordable machines in the Nespresso realm. It is slightly taller than the Inissia and more stylish. It is also sturdier, and has more parts made of metal than the Inissia. It is rated at 4.8 stars on the Nespresso website.
Nespresso offers 17 different coffee capsules to choose from plus assorted flavored versions, decafes, and the occasional special roast coffee, all rated by intensity. A variety pack comes with the machine, and after that you will want to register your machine at Nespresso.com and buy your capsules online from Nespresso. They source 80% of their coffees from AAA rated sustainable farms, and they provide postage paid envelopes to recycle your used coffee pods. I have always had exceptional customer service from Nespresso, and they stand behind their machines. If you get hooked on this espresso and want to upgrade your machine later, you can always take advantage of members only sales at Nespresso.com.
The only downside to this machine is the cost of the capsules. The cost is steadily going up. When I bought my first Nespresso Pixie the capsules were fifty cents apiece and now the cost is seventy cents per pod. Kinda like buying the cheap, feature laden printer only to find out the ink costs more than the price of silver.


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Karla Hirkaler Makeup Artist
danielleismsMakeup Artist Female Orlando, Florida, US
My Website: Danielle Rutherford - Makeup Artist
Mayhem # 3104906
About MeMy name is Danielle and I am professional makeup artist with over two years of experience. I have been a freelance artist for MAC Cosmetics and currently work as a freelance artist for NARS Cosmetics.
I have a passion for beauty, bridal, and runway makeup, but appreciate simplicity and highlighting natural beauty.
I am looking to make some great connections and build my portfolio. Please contact me here or at my website at daniellerutherford.com xx
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Karla Hirkaler Makeup Artist
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Rasheed Wallace Lakers
February 25, 2012 by staff
Rasheed Wallace Lakers, Former Portland Trail Blazers forward Rasheed Wallace, who hasn't played since Game 7 of the 2010 NBA Finals, will come out of retirement to sign with the Los Angeles Lakers, according to CSN New England.
Reports surfaced last month that Wallace was serious about returning to the game.
The big question with Wallace, 37, given his status as one of the most skilled big men of his era and ability to shoot and defend, is whether he's in shape to play. It's the same question that dogged him during his final season with the Boston Celtics, who, according to CSN, had no interest in bringing him back. That apparently is not an issue—Wallace has reportedly worked out hard and is in better shape than he was before his retirement.
If Wallace indeed signs with the Lakers, the next question becomes whether the team is bringing him in as a potential replacement for Pau Gasol, who has been the subject of trade rumors and drama for the entire season. Lakers GM Mitch Kupchak said Monday that the team would continue exploring trade proposals after Kobe Bryant stated that it was time for the team to either move Gasol or take him off the block.
Gasol, in his 11th season is averaging a career-low 16.6 points and has said the rumors have bothered him. One Western Conference executive told Hoopsworld that the Lakers are overvaluing him.
"I doubt Pau goes anywhere," the executive said. "I love Pau, but the Lakers are asking for way too much."
Additionally, one front-office executive source told CSN that Wallace's days as a starter are over—a fact that likely means that Gasol will be unaffected.
"His days as a starter in this league are gone," said the source. "I think he knows that, and so do the Lakers. But think about it. Of the big men that are available, is there one that's really better? And if he's gotten himself in shape, adding him becomes a huge get for them."
In 15 seasons with Washington, Portland, Atlanta, Detroit and Boston, Wallace averaged 14.6 points and 6.7 rebounds. In his eight seasons in Portland, Wallace averaged 16.8 points and 6.9 rebounds.
Please feel free to send if you have any questions regarding this post , you can contact on
Disclaimer: The views expressed on this site are that of the authors and not necessarily that of U.S.S.POST.


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Mr. Thomas Lorain
Paris, Paris IDF - France
No approved endorsements
About Mr. Thomas Lorain
14 years of music business experience and international development. Always looking for new ideas, partners and new business models.
If you notice offensive or incorrect information, please contact us.
Mr. Morvan Boury
VP Marketing Service@
EMI Music
Miss Geraldine Noel
Music Export manager


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- Category: Indian Law
- #53945Hi,
Yes, buyer will buy your property though you will have duplicate copy of the land documents because that copy will be issued by the registration office of your area. To get the certified duplicate copy of the document you have to go through following procedure:
1. file the compliant to nearest police station about lost of property documents. Get the copy of FIR
2. give public notice in the local news paper. Here, you have to take help of any local lawyer for preparing public notice.
3. apply to concerned registration office for certified duplicate copy of the document. Attaché your identity proof, FIR and some other old documents proving that land is owned by you for eg. Electricity bill or water bill etc.
Best regards,
- #53976Hello
Do not worry. If you have lost your original documents then you should make a police report. You can get a copy of FIR and then you can apply for a duplicate copies of the land documents. If your land is in the municipal limits then you can obtains TS-1 certificate from corporation. Otherwise you can visit to the Patwari of your land (area). He can give you a copy of Furd. With this you can get easily the duplicate registration of the land.
With best regards
Dinesh Sood
- #54045Thank you Vidya and Dinesh.
Tips for Healthy Life
- #57521Yes, buyer will buy your property though you will have duplicate copy of the land documents because that copy will be issued by the registration office of your area. And to get duplicate copy, first, file a police complaint and then go for a public notice in 1 English newspaper and 1 local newspaper. Now,in case, you have lost documents like Khata Certificate, Mutation Registrar, etc then you can apply to the revenue officer and collect the same. But if you have lost the originals sale deeds and old title deeds then apply for a certified copy. And also, ask your builder to provide you the copy of allotment, receipts and letters. I am sure it must be sounding a very complicated task to you. Believe me..it is indeed quite complicated as I've been through similar situation. I really had a tough time getting duplicate copy and was wishing for some service that would have managed my documents. Hey, You know what..i just came across this page on facebook 'clip to click', where members were discussing about launch of some service that would provide facility of individual document management.


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Route 66 GPS Attractions Guide instantly transforms your compatible Garmin GPS into a travel assistant to U.S. Route 66.
Learn More
Commercially used for years, the Route 66 GPS Turn By Turn software turns your Garmin Zumo™ into a virtual Route 66 tour guide.
Copyright © 2010-2017 River Pilot, LLC. All Rights Reserved. Privacy Policy. Return Policy


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|Pic Holie
Pic Holie (ピック・ホリィ Pikku Horii?) was a character set to appear in the cancelled video game, Mega Man Legends 3.
Pic would have been the Bright Bats' self-proclaimed information gatherer. Always scampering around town, he often came back with random junk parts he had picked up on his outing. That said, his findings were rarely of any use, and the gang's hangout was littered with his collected garbage, which were then used by Grill. His speech was a little rough around the edges. [1]
|Mega Man Legends series
|Main characters
| Mega Man Volnutt • Roll Caskett • Barrell Caskett • Data • Tron Bonne • Teisel Bonne • Bon Bonne • Servbots • Glyde • Birdbots
Lex Loath • Denise • Von Bluecher • Bola • Klaymoor • MegaMan Juno • Sera • Yuna • Gatz • Geetz • The Master
| Mega Man Legends • Mega Man Legends 2 •
The Misadventures of Tron Bonne • Rockman DASH: 5tsu no Shima no Daibouken!
Rockman DASH Golf • Kobun ga Tobun? • Oshioki Kobun • Kokkai Kobun • Roll-chan no 15 Panel
|Related items
| Flutter • Gesellschaft • Gustaff • Locations • Reaverbot • Refractor • Sulphur-Bottom • Support Car
Terms • Mega Man Volnutt's equipment


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Need a Chicken Pox Titer in Chowchilla, CA? Simply order online 24/7 and get a fast, affordable Chicken Pox Titer at a lab near you (Find More Locations):
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The Chicken Pox Titer is a blood test used to prove immunity to Chicken Pox. People in Chowchilla, CA get the Chicken Pox Titer for general screening or for credentialing for work or school.
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Our Chicken Pox Titer price includes the doctor's order that you need to get tested in Chowchilla, CA, all lab fees and taxes, and a pdf copy of your results. For current prices, please CLICK HERE.
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Bouazza relishing Gunners test
By Laurent Picard
Last Updated: 01/01/70 1:00am
Watford striker Hameur Bouazza is hoping to carve out a successful career in England.
Watford striker Hameur Bouazza is hoping to emulate his idol Thierry Henry and carve out a successful career in England.
The 20-year-old Frenchman has told skysports.com he will start for The Hornets against Arsenal on Saturday, and he is relishing the chance to go head-to-head with Henry.
"Thierry Henry is somebody for France," he said. "I have already met with him, thanks to my agent.
"We talked a little, but it will be weird to meet him again, on the pitch.
"I will start the match at The Emirates Stadium."
Bouazza has taken enormous confidence from his early Premiership performances, but knows that it will be difficult for him to make a big impact in such a competitive league.
"Before being a pro I used to watch the stars on TV, and playing against Cristiano Ronaldo, Louis Saha and Mikael Silvestre has been great," he enthused.
"I try to tell myself that if we are on the same pitch, it means we are equal.
"I am so hungry for football, so I am prepared to do everything I can.
"A lot of players want to join The Premiership, from Germany, Spain, Italy.
"But look at Hernan Crespo or Andrei Shevchenko. It is not that easy to succeed here."
Bouazza also underlined his commitment to Watford by revealing that he was poised to sign a new deal with the club.
"I have shown the Watford coach (Aidy Boothroyd) I want to stay, and I am about to sign a new contract extension," he said.
"I don't know if I will spend all my career in England, we will see, but for the moment I am focused on Watford."


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One ranking, not the only one
Says of Georgia, "for four years in a row, we are the No. 1 state to do business in."
— PolitiFact Georgia
on Wednesday, July 19th, 2017
That's for all Texas taxes
"Sixty-two percent of all (Texas) property taxes are paid by businesses."
— PolitiFact Texas
on Friday, May 5th, 2017
Claim is on target
Small businesses "create two out of every three American jobs."
— PolitiFact Missouri
on Friday, March 17th, 2017
Trump has been all over the map
"First, Donald Trump said wages are too high, and both Donald Trump and Mike Pence think we ought to eliminate the federal minimum wage."
— PolitiFact National
on Tuesday, October 4th, 2016
Claim is a pizza work
"That's legal: If you find out about somebody else's salary even if you're doing exactly the same job, you can be retaliated against, including being fired, in most places."
— PolitiFact National
on Friday, September 9th, 2016