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Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.
Multiple sclerosis (MS) is known for the great variability of its clinical presentations, spanning the relapsing-remitting course with a subsequent secondary progressive phase, primary progressive course and relapsing-progressive course. The rate of disability accumulation varies from a lack of disease activity (benign MS) to rapidly progressing (malignant) MS [1] with a range of possible neurological manifestations. Therefore, the view of MS as a heterogeneous entity resulting from a number of inter-related etiopathogenetic cascades has been receiving increasing scientific attention [2-4]. The role of the immune system is likely to be pivotal in the disease pathogenesis, however, direct causality is yet to be established [5,6]. Surrogate markers such as magnetic resonance imaging (MRI), optic coherent tomography and susceptibility genes may elucidate the great clinical variability arising from the complex etiopathogenesis. On the diagnostic level, these might help to identify the specific subtypes of disease in individual patients, predict the future MS course, and develop individually tailored therapeutic regimens [7,8].
The currently available therapies, which are based mainly on their anti-inflammatory properties, are imperfect, with a number of patients showing only sub-optimal control over the MS activity [9]. It is therefore important that clinicians are able to predict the future response to treatment in individual patients early after disease onset in order to allow for the most appropriate treatment to be chosen [10]. Furthermore, the treatment, once administered, needs to be monitored to verify its efficacy. In both instances, surrogate markers may play significant roles [11,12]. Among different surrogate markers, MRI has been the only one used routinely in clinical practice. The traditional view of MS as a disease affecting predominantly white matter (WM) was driven by the higher sensitivity of the conventional MRI techniques to the WM changes [13-15]. However, these changes proved to be insufficient to explain the broad spectrum of neurological and psychological manifestations of MS satisfactorily [16-22]. Novel MRI techniques with improved sensitivity to grey matter (GM) changes [23-28] have shown that the GM damage is more prevalent than first estimated [29-34], that it may even precede development of the WM damage [35], and that it is significantly associated with physical and cognitive impairment [11,12,31,36-47]. The aim of this review is to summarise the current knowledge of the GM damage in MS and of its clinical implications.
Assessing grey matter pathology
Both GM atrophy [11,34,38,41,42,44,48] and GM lesions [29-32,49-52] were demonstrated in cerebral cortex and deep GM structures using MRI supported by histological studies [32,53-56]. A body of work suggested that GM atrophy occurs early in relapsing-remitting as well as primary progressive MS [15,38,57-59]. Its progression was shown to be more prominent compared to WM atrophy, which is in contrast to some of the earlier works [12,33,34,44,60]. GM atrophy becomes more evident with the progression of MS [12,34,36] and in the chronic stages might even drive total brain atrophy [12]. Its relation to the WM changes, however, has not been sufficiently explained [52,61,62]. GM atrophy has been associated with several MHC II alleles [63], which are known genetic risk factors in MS [6,64]. This all implies that GM atrophy may play an important role in the pathogenesis of MS.
It is known that GM atrophy is not distributed homogeneously. Temporal and frontal cortex (including motor areas) can be affected predominantly, particularly early in the disease course [12,33,39,65-70]. The subcortical GM also shows marked atrophy, especially in the thalamus, basal ganglia (caudate and striatum) and the infratentorial structures [58,66,71,72]. As a result, cortico-subcortical connections might suffer significant damage [73].
According to the original pathological study of Brownell and Hughes, GM lesions comprise 26% of all lesions identified in the central nervous system (CNS) [29]. Cortical lesions occur early in clinically isolated syndrome (CIS) and relapsing-remitting MS, as well as in primary progressive MS (36%, 64% and 81% of patients, respectively) and increase in number and size with progression of the disease [30,31,74]. Cortical lesions are most common in the frontal and temporal cortex, predominantly affecting the motor (30-40%) and cingulate areas (10%) [75]. Among the subcortical GM, the structures most affected are the thalamus, basal ganglia, hypothalamus, hippocampus, cerebellum and spinal cord [76-80]. Compared to WM lesions, inflammation is less pronounced [51] and the blood-brain barrier is not disrupted in GM lesions [81]. Interestingly, T-cell mediated autoimmunity directed against contactin-2, which is present specifically within the GM, was identified as a factor contributing to the GM pathology in MS [3].
Sensitivity of the conventional MRI methods for GM lesions is low compared to WM lesions [32,82]. This improves with alternative techniques, such as double inversion recovery (DIR) [25,28,83] and its combination with phase-sensitive inversion recovery [27], T1-weighted gradient-recalled-echo [23] and higher field-strength MRI [24,26]. Another promising approach is the combination of the conventional MRI techniques with magnetisation transfer ratio [73,84]. Furthermore, diffusion tensor imaging has the potential to uncover progressive microstructural changes in normal-appearing GM [85]. Functional changes in MS can be examined using functional MRI to study re-organisation of the cortex, positron emission tomography to establish activation of microglia, or continuous arterial spin labelling to analyse brain perfusion [86-88]. Despite their promising results, the non-conventional MRI techniques have so far found only a limited use in routine clinical practice, partly due to their sparse availability and high technological and time requirements, and partly due to limited reproducibility of their outcomes [89].
Clinical correlates of GM impairment
Abnormalities of GM are present early in CIS [90-95] and evolve with its progression to definite MS [11,96-98]. Numerous works have shown that the changes in GM are closely associated with both physical disability and cognitive impairment (see Table 1) [31,33,37,68,99-101].
Table 1. Selected works studying grey matter changes and their relations to physical and cognitive impairment in MS
Physical disability
GM atrophy
It is known that GM atrophy is correlated with physical disability and its progression (r = 0.47 - 0.59) [12,36,39,102,103]. According to a number of studies, this relation is stronger than that of WM matter changes [33,57,67,99,100]. Fisniku and co-workers showed that GM atrophy, unlike WM atrophy, increases in patients with moderate disability [Expanded Disability Status Scale (EDSS) > 3] [36]. This view is further supported by the fact that the GM atrophy rate is accelerated upon conversion from CIS to the relapsing-remitting and secondary progressive stages (3.4× and 14× the normal rates, respectively), while WM atrophy remains stable throughout the MS course (3× the normal rate) [11,12]. The association of GM atrophy with disability becomes even stronger in primary progressive MS [33]. All this suggests that the GM changes could be more representative of the progressive damage to the CNS and the resulting physical disability than the WM damage. However, it is worth noting that also some contrasting results have been reported [15]. These opposing conclusions may relate to inequalities in studied cohorts, such as differences in disease stages or subtypes.
GM lesions
Apart from the GM atrophy, cortical and subcortical inflammatory (T2 hyperintense) GM lesions also contribute to the overall disability in MS [104,105]. They show mild correlation with EDSS and moderate correlation with its changes in time [31]. Similar to the atrophy, primary progressive MS shows more pronounced accumulation of the GM lesions, parallel with accumulation of the physical disability [30]. On the other hand, in a benign form of MS with only a modest disability after long disease duration, the GM lesions are sparse [106].
T2 hypointense lesions have also been reported in MS. They may represent iron deposits and foci of brain degeneration [107,108], predominantly located within the thalamus, striatum and rolandic cortex [107-109]. Similar to the T2 hyperintense lesions, T2 hypointense lesions are associated with physical disability [43,109-111] as well as cognitive impairment [112], and are predictive of future brain atrophy [108,113].
Regional GM changes
Among the regional GM changes, it is in particular the cortical atrophy which is thought to be associated with physical disability [13,15,33,100]. However, structural changes within the thalamus could also play role in the accumulation of disability [114]. It was suggested that MS-associated fatigue could be secondary to the regional atrophy of the fronto-parietal cortex, striatum and thalamus [115-118] as well as the higher overall GM lesion burden [69,119]. On the other hand, impaired gait may be associated with the damage to the dentate nucleus [43]. Another co-morbidity of MS - restless legs syndrome - is probably related to the changes in the cervical spinal cord [120], where demyelination of GM is more extensive than that of WM [77]. Apart from the routinely evaluated signs of the physical disability, the GM lesions are likely to contribute to the increased epileptic activity [121] which occurs in 2.9% of patients with MS (i.e. its prevalence is 3-6× higher compared to healthy population) [122-124]. Yet, it is not known whether the severity of physical impairment is proportional to the GM lesion volume or if it depends more on the topography of the focal GM damage.
GM reorganisation
Besides the limited regenerative capacity of the CNS [125], adaptation of neural networks represents important compensatory mechanism of the damaged CNS. Cortical reorganisation, as shown by a number of studies with functional MRI, occurs early in MS, but its extent varies greatly among patients. It can be visualised as a non-normal cortical activation pattern, elicited by standardised motor and cognitive tasks [126-133]. For instance, during motor processing, recruitment of higher (supplementary) areas may be seen even with simple movements in MS patients but not in healthy subjects [129,130,134]. Similar functional reorganisation takes place in the cervical spinal cord [135]. This can be interpreted as compensation for damage inflicted by the demyelination and neuronal loss. It is possible that more extensive (or efficient) compensation and axonal regeneration contribute to a less severe course of MS and slower accumulation of the CNS structural damage [106,134].
Evaluation of disability
Research of functional outcomes of the structural changes in MS depends on the ability of clinicians to quantify physical and cognitive impairment in MS patients. Two scales, EDSS and Multiple Sclerosis Functional Composite (MSFC), have been used most commonly to evaluate the physical impairment in clinical practice and in research. Both of these scales quantify the extent of disability only imperfectly [136]. For EDSS, this is attributed to suboptimal inter-rater reproducibility, lack of weighted functional sub-scores and omission of psychological assessment [137], while for MSFC, this is due to practice effects, variations in reference populations, omission of visual assessment and lack of accepted definition of a clinically meaningful change [138]. EDSS mainly evaluates the physical component of the impairment, with the emphasis on ambulation, assessing the cognitive impairment only marginally. On the other hand, MSFC is a more complex scale with objective evaluation of ambulation (timed 25-foot walk test), fine motor skills (9-hole peg test) and cognition (3-second Paced Auditory Serial Addition Test). It was suggested that MSFC may better correlate with GM atrophy than EDSS [12,36]. Furthermore, it is possible that EDSS is more sensitive to disability progression in patients with mild physical disability, while being less sensitive to the progression in patients with more severe disability [139]. This raises concerns about the value of EDSS in secondary progressive MS. In any case, instruments assessing the physical disability reliably at all stages and in all courses of MS are critical for accurate evaluation of the descriptive and prognostic value of the GM changes.
Cognitive impairment
Cognitive impairment is highly prevalent in MS, affecting 40-65% of patients with all disease courses and in all its clinical stages [140]. Although the character and severity of the cognitive impairment vary widely among the patients, information processing speed, attention, recent and long-term memory, executive functions and visuospatial abilities seem to be the most affected domains, whereas general intelligence, language and certain aspects of memory (short-term capacity and implicit memory) are spared, and overt dementia is rare in MS [141-143]. In addition, in patients with disease onset before the age of 18, impairment of expressive language and visuomotor integration were described [144]. This suggests that even in young patients the damage to the CNS may exceed its plasticity. Overall, the extreme variability of the cognitive impairment may depend on several factors, such as patient age, gender, age at disease onset, level of education and cognitive reserve [145,146].
GM vs. WM changes
Even though significant correlations between the amount and the regions of the WM atrophy vs. the degree and pattern of cognitive impairment were shown [147], studies failed to explain the full array of cognitive impairment by the WM damage only [148]. A range of specific cognitive deficits, such as memory impairment, low information processing speed and attention deficits, could be better explained by the cortical GM lesions rather than the subcortical WM lesions [148]. Changes in the GM might therefore add to our understanding of the causality of the cognitive impairment in MS. For example, more widespread atrophy and hypometabolism of GM can be found in the cognitively impaired patients than in those cognitively intact [149,150]. Moreover, it is of interest that the cognitive impairment is more prominent at the time of conversion from the relapsing-remitting to the secondary progressive course [151,152], which is also marked by accelerated degeneration of the cerebral GM [12]. In fact, a number of works provided evidence of a strong association between GM impairment (lesions and atrophy) and global or selective cognitive disability in MS [40,68,101,142,149,153], which may imply a causative relation [148].
Regional GM changes
A pattern of widespread cortical thinning was found in cognitively impaired patients with relapsing-remitting MS [149,154]. Even a cortical variant of MS was described in those with the cognitive impairment among the initial manifestations of MS [155,156]. It was shown that neocortical atrophy is related to the impairment of verbal memory [40,65,68,153], visual episodic and working memory [68], verbal fluency [40,101], attention/concentration [40] and processing speed [65,70,157]. It may also be responsible for subtle personality changes observed in MS patients, such as disinhibition and euphoria [153,158]. More specifically, atrophy of the prefrontal, precentral and superior parietal cortex is related to the decreased processing speed and impaired calculation abilities [70]. Left frontal atrophy occurs in patients with impaired auditory/verbal memory, while right frontal atrophy is related to impaired visual episodic and working memory [68]. Atrophy of the mesial temporal cortex is associated with decreased processing speed and impaired episodic and verbal memory [159,160]. Atrophy of the subcortical GM structures can be evaluated either directly or indirectly - using enlargement of the third ventricle as a marker [68,154]. Of the subcortical GM, the most relevant are the atrophy, structural changes and altered metabolism of the thalamus, which are linked with deterioration in multiple cognitive domains [114,144,150,154,157,161,162].
Compared to GM atrophy, there is considerably less evidence to support contribution of demyelinating lesions of GM to cognitive impairment. The volume of the cortical lesions shows only a modest association with cognitive impairment, while an increase in the lesion volume seems to be moderately associated with cognitive deterioration [31,37,163,164]. More specifically, lesions in the medial frontal and temporal cortex seem to correlate with impaired memory [164].
Overall, it can be speculated that the cognitive decline observed in MS patients results from focal inflammatory lesions and widespread GM loss. Despite the fact that the neuropsychological profiles of MS patients cannot be defined as either purely "cortical" or "subcortical" [165], it is likely that it is the impairment of the cortical GM which determines the level and character of cognitive dysfunction.
GM as a surrogate marker
Objective indicators of MS activity as well as predictors of future disease course and treatment efficacy applicable in individual patients are crucial for making appropriate therapeutic decisions in routine clinical practice. A number of works have addressed these issues, and several markers, both clinical and paraclinical, have been suggested [7,21,166-169]. Yet, accuracy of the MRI markers, particularly when used in individual patients, is only limited [16,170,171].
Marker of MS activity
According to the existing evidence, changes in GM might represent a reliable marker of disease activity and of CNS damage. The relatively less pronounced inflammation within GM is likely to result in lesser fluctuations of its changes triggered by the relapsing inflammatory activity [51]. Moreover, focal oedema and treatment-associated pseudoatrophy, which may mask the changes reflecting the activity of MS, are known to be less evident in GM [172,173]. Therefore GM lesions and atrophy, rather than WM changes, might better reflect long-term changes which drive the accumulation of disability [174].
In fact, assessment of GM lesions improves the specificity and accuracy of MRI diagnostic criteria [175]. At the same time, GM atrophy correlates closely with the progression of CIS to clinically definite MS [11,12,39,176]. Furthermore, both GM lesions and GM atrophy can be used to predict this conversion [96,175]. Long-term accumulation of disability is also predicted by the diffuse changes in the GM [36,177]. It can be speculated that an even better prognostic value may be achieved with assessment of regional GM atrophy.
Monitoring of treatment efficacy
For the reasons discussed above, the impairment of GM has the potential to become an important marker of the efficacy of immunomodulatory remedies [21]. On the other hand, the less inflammatory nature of GM damage [51,178,179] and better preservation of the blood-brain barrier within altered GM [180] may diminish the response of GM to immunomodulatory therapy. Calabrese and co-workers demonstrated a decrease in accumulation of GM lesions and cortical atrophy in patients treated with disease modifying drugs, and reported a more pronounced effect of subcutaneous interferon β compared to intramuscular interferon β and glatiramer acetate [181]. Zivadinov and co-authors observed ameliorated progression of GM atrophy in patients treated with interferon β [182]. In contrast, Benfeldt and co-workers reported more pronounced atrophy in the fronto-temporal, cingulate and cerebellar cortex in patients treated with interferon β. It is therefore apparent that more work evaluating the effect of immunomodulation on the changes in GM is required.
The growing body of evidence supports the view of MS as a disease not only of WM but also of GM. The mechanisms responsible for the inter-individual variation in the extent of GM and WM pathology are largely unknown, and their identification will significantly contribute to the understanding of the MS etiopathogenesis. On the diagnostic level, GM atrophy and lesions provide information complementary to the conventional MRI variables and further improve correlation between the radiological and clinical variables [118,183]. Thus, GM pathology may not only serve as a new marker for the existing immunomodulatory therapies but may also provide a potential target for novel therapies.
CIS: clinically isolated syndrome; CNS: central nervous system; EDSS: Expanded Disability Status Scale; GM: grey matter; MRI: magnetic resonance imaging; MS: multiple sclerosis; MSFC: Multiple Sclerosis Functional Composite; WM: white matter
Competing interests
Dana Horakova has received speaker honoraria and consultant fees from Biogen Idec, Merck-Serono, Bayer Shering and Teva, as well as support for research activities from Biogen Idec.
Tomas Kalincik has received compensation for travel and honoraria from Biogen Idec, Sanofi Aventis, Teva and Merck-Serono.
Jana Blahova Dusankova has received speaker honoraria and compensation for travel from Biogen Idec, Bayer Shering, Merck-Serono and Novartis.
Ondrej Dolezal has received speaker honoraria and compensation for travel from Biogen Idec, Merck-Serono and Novartis.
The authors have received financial support from the Czech Ministry of Health [MSM 0021620849].
Authors' contributions
DH prepared the Introduction and Physical disability sections and Table 1, and reviewed the manuscript. TK prepared the Physical disability section and Table 1, and edited and reviewed the manuscript. JBD prepared the Cognitive impairment section and reviewed the manuscript. OD prepared the Assessing grey matter pathology section and reviewed the manuscript. All authors read and approved the final manuscript.
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Bermel RA, Innus MD, Tjoa CW, Bakshi R: Selective caudate atrophy in multiple sclerosis: a 3D MRI parcellation study.
Cifelli A, Arridge M, Jezzard P, Esiri MM, Palace J, Matthews PM: Thalamic neurodegeneration in multiple sclerosis.
Ciccarelli O, Werring DJ, Wheeler-Kingshott CA, Barker GJ, Parker GJ, Thompson AJ, Miller DH: Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations.
Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, Morra A, Rinaldi L, Romualdi C, Perini P, et al.: Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis.
Calabrese M, Battaglini M, Giorgio A, Atzori M, Bernardi V, Mattisi I, Gallo P, De Stefano N: Imaging distribution and frequency of cortical lesions in patients with multiple sclerosis.
Geurts JJ, Bo L, Roosendaal SD, Hazes T, Daniels R, Barkhof F, Witter MP, Huitinga I, van der Valk P: Extensive hippocampal demyelination in multiple sclerosis.
Gilmore CP, Bo L, Owens T, Lowe J, Esiri MM, Evangelou N: Spinal cord gray matter demyelination in multiple sclerosis-a novel pattern of residual plaque morphology.
Huitinga I, De Groot CJ, Van der Valk P, Kamphorst W, Tilders FJ, Swaab DF: Hypothalamic lesions in multiple sclerosis.
Vercellino M, Plano F, Votta B, Mutani R, Giordana MT, Cavalla P: Grey matter pathology in multiple sclerosis.
Calabrese M, Mattisi I, Rinaldi F, Favaretto A, Atzori M, Bernardi V, Barachino L, Romualdi C, Rinaldi L, Perini P, et al.: Magnetic resonance evidence of cerebellar cortical pathology in multiple sclerosis.
van Horssen J, Brink BP, de Vries HE, van der Valk P, Bo L: The blood-brain barrier in cortical multiple sclerosis lesions.
Dolezal O, Dwyer MG, Horakova D, Havrdova E, Minagar A, Balachandran S, Bergsland N, Seidl Z, Vaneckova M, Fritz D, et al.: Detection of cortical lesions is dependent on choice of slice thickness in patients with multiple sclerosis.
Rinaldi F, Calabrese M, Grossi P, Puthenparampil M, Perini P, Gallo P: Cortical lesions and cognitive impairment in multiple sclerosis.
Davies GR, Altmann DR, Hadjiprocopis A, Rashid W, Chard DT, Griffin CM, Tofts PS, Barker GJ, Kapoor R, Thompson AJ, et al.: Increasing normal-appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing-remitting multiple sclerosis.
Oreja-Guevara C, Rovaris M, Iannucci G, Valsasina P, Caputo D, Cavarretta R, Sormani MP, Ferrante P, Comi G, Filippi M: Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study.
Versijpt J, Debruyne JC, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, et al.: Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study.
Rashid W, Parkes LM, Ingle GT, Chard DT, Toosy AT, Altmann DR, Symms MR, Tofts PS, Thompson AJ, Miller DH: Abnormalities of cerebral perfusion in multiple sclerosis.
Rocca MA, Pagani E, Ghezzi A, Falini A, Zaffaroni M, Colombo B, Scotti G, Comi G, Filippi M: Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain.
Geurts JJ, Roosendaal SD, Calabrese M, Ciccarelli O, Agosta F, Chard DT, Gass A, Huerga E, Moraal B, Pareto D, et al.: Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI.
Audoin B, Zaaraoui W, Reuter F, Rico A, Malikova I, Confort-Gouny S, Cozzone PJ, Pelletier J, Ranjeva JP: Atrophy mainly affects the limbic system and the deep grey matter at the first stage of multiple sclerosis.
Calabrese M, Atzori M, Bernardi V, Morra A, Romualdi C, Rinaldi L, McAuliffe MJ, Barachino L, Perini P, Fischl B, et al.: Cortical atrophy is relevant in multiple sclerosis at clinical onset.
Fisniku LK, Altmann DR, Cercignani M, Tozer DJ, Chard DT, Jackson JS, Miszkiel KA, Schmierer K, Thompson AJ, Miller DH: Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis.
Henry RG, Shieh M, Amirbekian B, Chung S, Okuda DT, Pelletier D: Connecting white matter injury and thalamic atrophy in clinically isolated syndromes.
Henry RG, Shieh M, Okuda DT, Evangelista A, Gorno-Tempini ML, Pelletier D: Regional grey matter atrophy in clinically isolated syndromes at presentation.
Roosendaal SD, Bendfeldt K, Vrenken H, Polman CH, Borgwardt S, Radue EW, Kappos L, Pelletier D, Hauser SL, Matthews PM, et al.: Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability.
Calabrese M, Rinaldi F, Mattisi I, Bernardi V, Favaretto A, Perini P, Gallo P: The predictive value of gray matter atrophy in clinically isolated syndromes.
Raz E, Cercignani M, Sbardella E, Totaro P, Pozzilli C, Bozzali M, Pantano P: Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging.
Rocca MA, Agosta F, Sormani MP, Fernando K, Tintore M, Korteweg T, Tortorella P, Miller DH, Thompson A, Rovira A, et al.: A three-year, multi-parametric MRI study in patients at presentation with CIS.
Bakshi R, Benedict RH, Bermel RA, Jacobs L: Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative magnetic resonance imaging and relationship to clinical findings.
Sanfilipo MP, Benedict RH, Sharma J, Weinstock-Guttman B, Bakshi R: The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction.
Amato MP, Portaccio E, Goretti B, Zipoli V, Battaglini M, Bartolozzi ML, Stromillo ML, Guidi L, Siracusa G, Sorbi S, et al.: Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis.
Horakova D, Dwyer MG, Havrdova E, Cox JL, Dolezal O, Bergsland N, Rimes B, Seidl Z, Vaneckova M, Zivadinov R: Gray matter atrophy and disability progression in patients with early relapsing-remitting multiple sclerosis: a 5-year longitudinal study.
Bonati U, Fisniku LK, Altmann DR, Yiannakas MC, Furby J, Thompson AJ, Miller DH, Chard DT: Cervical cord and brain grey matter atrophy independently associate with long-term MS disability.
Hayton T, Furby J, Smith KJ, Altmann DR, Brenner R, Chataway J, Hughes RA, Hunter K, Tozer DJ, Miller DH, et al.: Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis.
Rovaris M, Judica E, Sastre-Garriga J, Rovira A, Sormani MP, Benedetti B, Korteweg T, De Stefano N, Khaleeli Z, Montalban X, et al.: Large-scale, multicentre, quantitative MRI study of brain and cord damage in primary progressive multiple sclerosis.
Calabrese M, Filippi M, Rovaris M, Bernardi V, Atzori M, Mattisi I, Favaretto A, Grossi P, Barachino L, Rinaldi L, et al.: Evidence for relative cortical sparing in benign multiple sclerosis: a longitudinal magnetic resonance imaging study.
Drayer B, Burger P, Hurwitz B, Dawson D, Cain J: Reduced signal intensity on MR images of thalamus and putamen in multiple sclerosis: increased iron content?
Bakshi R, Dmochowski J, Shaikh ZA, Jacobs L: Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients.
Bakshi R, Shaikh ZA, Janardhan V: MRI T2 shortening ('black T2') in multiple sclerosis: frequency, location, and clinical correlation.
Neema M, Stankiewicz J, Arora A, Dandamudi VS, Batt CE, Guss ZD, Al-Sabbagh A, Bakshi R: T1- and T2-based MRI measures of diffuse gray matter and white matter damage in patients with multiple sclerosis.
Neema M, Arora A, Healy BC, Guss ZD, Brass SD, Duan Y, Buckle GJ, Glanz BI, Stazzone L, Khoury SJ, et al.: Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis.
Brass SD, Benedict RH, Weinstock-Guttman B, Munschauer F, Bakshi R: Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.
Bermel RA, Puli SR, Rudick RA, Weinstock-Guttman B, Fisher E, Munschauer FE, Bakshi R: Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity.
Tovar-Moll F, Evangelou IE, Chiu AW, Richert ND, Ostuni JL, Ohayon JM, Auh S, Ehrmantraut M, Talagala SL, McFarland HF, et al.: Thalamic involvement and its impact on clinical disability in patients with multiple sclerosis: a diffusion tensor imaging study at 3T.
Niepel G, Tench Ch R, Morgan PS, Evangelou N, Auer DP, Constantinescu CS: Deep gray matter and fatigue in MS: a T1 relaxation time study.
Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G, Comi G: Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis.
Calabrese M, Rinaldi F, Grossi P, Mattisi I, Bernardi V, Favaretto A, Perini P, Gallo P: Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing-remitting multiple sclerosis.
Poonawalla AH, Datta S, Juneja V, Nelson F, Wolinsky JS, Cutter G, Narayana PA: Composite MRI scores improve correlation with EDSS in multiple sclerosis.
Sepulcre J, Masdeu JC, Goni J, Arrondo G, Velez de Mendizabal N, Bejarano B, Villoslada P: Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways.
Manconi M, Rocca MA, Ferini-Strambi L, Tortorella P, Agosta F, Comi G, Filippi M: Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage.
Calabrese M, De Stefano N, Atzori M, Bernardi V, Mattisi I, Barachino L, Rinaldi L, Morra A, McAuliffe MM, Perini P, et al.: Extensive cortical inflammation is associated with epilepsy in multiple sclerosis.
Poser CM, Brinar VV: Epilepsy and multiple sclerosis.
Moreau T, Sochurkova D, Lemesle M, Madinier G, Billiar T, Giroud M, Dumas R: Epilepsy in patients with multiple sclerosis: radiological-clinical correlations.
Sokic DV, Stojsavljevic N, Drulovic J, Dujmovic I, Mesaros S, Ercegovac M, Peric V, Dragutinovic G, Levic Z: Seizures in multiple sclerosis.
Meier DS, Weiner HL, Guttmann CR: Time-series modeling of multiple sclerosis disease activity: a promising window on disease progression and repair potential?
Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics 2007, 4(3):485-498.
Filippi M, Rocca MA, Falini A, Caputo D, Ghezzi A, Colombo B, Scotti G, Comi G: Correlations between structural CNS damage and functional MRI changes in primary progressive MS.
Lee M, Reddy H, Johansen-Berg H, Pendlebury S, Jenkinson M, Smith S, Palace J, Matthews PM: The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis.
Reddy H, Narayanan S, Arnoutelis R, Jenkinson M, Antel J, Matthews PM, Arnold DL: Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis.
Valsasina P, Rocca MA, Absinta M, Sormani MP, Mancini L, De Stefano N, Rovira A, Gass A, Enzinger C, Barkhof F, et al.: A multicentre study of motor functional connectivity changes in patients with multiple sclerosis.
Rico A, Zaaraoui W, Franques J, Attarian S, Reuter F, Malikova I, Confort-Gouny S, Soulier E, Pouget J, Cozzone PJ, et al.: Motor cortical reorganization is present after a single attack of multiple sclerosis devoid of cortico-spinal dysfunction.
Cader S, Cifelli A, Abu-Omar Y, Palace J, Matthews PM: Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis.
Parry AM, Scott RB, Palace J, Smith S, Matthews PM: Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine.
Audoin B, Ibarrola D, Ranjeva JP, Confort-Gouny S, Malikova I, Ali-Cherif A, Pelletier J, Cozzone P: Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS.
Giorgio A, Portaccio E, Stromillo ML, Marino S, Zipoli V, Battaglini M, Blandino A, Bartolozzi ML, Siracusa G, Amato MP, et al.: Cortical functional reorganization and its relationship with brain structural damage in patients with benign multiple sclerosis.
Agosta F, Valsasina P, Rocca MA, Caputo D, Sala S, Judica E, Stroman PW, Filippi M: Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis.
Goldman MD, Motl RW, Rudick RA: Possible clinical outcome measures for clinical trials in patients with multiple sclerosis.
Hobart J, Freeman J, Thompson A: Kurtzke scales revisited: the application of psychometric methods to clinical intuition.
Polman CH, Rudick RA: The multiple sclerosis functional composite: a clinically meaningful measure of disability.
Rudick RA, Lee JC, Nakamura K, Fisher E: Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS.
Patti F: Cognitive impairment in multiple sclerosis.
Rao SM: Neuropsychology of multiple sclerosis.
Tur C, Penny S, Khaleeli Z, Altmann D, Cipolotti L, Ron M, Thompson A, Ciccarelli O: Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.
Chiaravalloti ND, DeLuca J: Cognitive impairment in multiple sclerosis.
Till C, Ghassemi R, Aubert-Broche B, Kerbrat A, Collins DL, Narayanan S, Arnold DL, Desrocher M, Sled JG, Banwell BL: MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.
Amato MP, Goretti B, Ghezzi A, Lori S, Zipoli V, Moiola L, Falautano M, De Caro MF, Viterbo R, Patti F, et al.: Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up.
Benedict RH, Zivadinov R: Risk factors for and management of cognitive dysfunction in multiple sclerosis.
Amato MP, Zipoli V, Portaccio E: Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies.
Calabrese M, Rinaldi F, Grossi P, Gallo P: Cortical pathology and cognitive impairment in multiple sclerosis.
Calabrese M, Rinaldi F, Mattisi I, Grossi P, Favaretto A, Atzori M, Bernardi V, Barachino L, Romualdi C, Rinaldi L, et al.: Widespread cortical thinning characterizes patients with MS with mild cognitive impairment.
Blinkenberg M, Rune K, Jensen CV, Ravnborg M, Kyllingsbaek S, Holm S, Paulson OB, Sorensen PS: Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS.
Filippi M, Alberoni M, Martinelli V, Sirabian G, Bressi S, Canal N, Comi G: Influence of clinical variables on neuropsychological performance in multiple sclerosis.
Benedict RH, Carone DA, Bakshi R: Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis.
Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R: Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis.
Benedict RH, Bruce JM, Dwyer MG, Abdelrahman N, Hussein S, Weinstock-Guttman B, Garg N, Munschauer F, Zivadinov R: Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis.
Zarei M: Clinical characteristics of cortical multiple sclerosis.
Zarei M, Chandran S, Compston A, Hodges J: Cognitive presentation of multiple sclerosis: evidence for a cortical variant.
Batista S, Zivadinov R, Hoogs M, Bergsland N, Heininen-Brown M, Dwyer MG, Weinstock-Guttman B, Benedict RH: Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis.
Benedict RH, Hussein S, Englert J, Dwyer MG, Abdelrahman N, Cox JL, Munschauer FE, Weinstock-Guttman B, Zivadinov R: Cortical atrophy and personality in multiple sclerosis.
Benedict RH, Ramasamy D, Munschauer F, Weinstock-Guttman B, Zivadinov R: Memory impairment in multiple sclerosis: correlation with deep grey matter and mesial temporal atrophy.
Anderson VM, Fisniku LK, Khaleeli Z, Summers MM, Penny SA, Altmann DR, Thompson AJ, Ron MA, Miller DH: Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study.
Houtchens MK, Benedict RH, Killiany R, Sharma J, Jaisani Z, Singh B, Weinstock-Guttman B, Guttmann CR, Bakshi R: Thalamic atrophy and cognition in multiple sclerosis.
Hildebrandt H, Hahn HK, Kraus JA, Schulte-Herbruggen A, Schwarze B, Schwendemann G: Memory performance in multiple sclerosis patients correlates with central brain atrophy.
Roosendaal SD, Moraal B, Pouwels PJ, Vrenken H, Castelijns JA, Barkhof F, Geurts JJ: Accumulation of cortical lesions in MS: relation with cognitive impairment.
Bagnato F, Salman Z, Kane R, Auh S, Cantor FK, Ehrmantraut M, Gallo A, Ikonomidou VN, Ohayon J, Pellicano C, et al.: T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis.
Calabrese P, Penner IK: Cognitive dysfunctions in multiple sclerosis--a "multiple disconnection syndrome"?
Barkhof F, Calabresi PA, Miller DH, Reingold SC: Imaging outcomes for neuroprotection and repair in multiple sclerosis trials.
Tintore M, Rovira A, Rio J, Nos C, Grive E, Tellez N, Pelayo R, Comabella M, Sastre-Garriga J, Montalban X: Baseline MRI predicts future attacks and disability in clinically isolated syndromes.
Daumer M, Neuhaus A, Herbert J, Ebers G: Prognosis of the individual course of disease: the elements of time, heterogeneity and precision.
Rio J, Castillo J, Rovira A, Tintore M, Sastre-Garriga J, Horga A, Nos C, Comabella M, Aymerich X, Montalban X: Measures in the first year of therapy predict the response to interferon beta in MS.
Li DK, Held U, Petkau J, Daumer M, Barkhof F, Fazekas F, Frank JA, Kappos L, Miller DH, Simon JH, et al.: MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.
Zivadinov R, Leist TP: Clinical-magnetic resonance imaging correlations in multiple sclerosis.
Zivadinov R, Reder AT, Filippi M, Minagar A, Stuve O, Lassmann H, Racke MK, Dwyer MG, Frohman EM, Khan O: Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis.
Kelemen A, Dwyer MG, Horakova D, Vaneckova M, Havrdova E, Zivadinov R: Measurement of gray matter volume is less susceptible to pseudoatrophy effect than that of white matter or whole brain volume in patients with multiple sclerosis. Results from Avonex-Steroids-Azathioprine combination study.
Rovaris M, Gallo A, Valsasina P, Benedetti B, Caputo D, Ghezzi A, Montanari E, Sormani MP, Bertolotto A, Mancardi G, et al.: Short-term accrual of gray matter pathology in patients with progressive multiple sclerosis: an in vivo study using diffusion tensor MRI.
Filippi M, Rocca MA, Calabrese M, Sormani MP, Rinaldi F, Perini P, Comi G, Gallo P: Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis.
Brex PA, Jenkins R, Fox NC, Crum WR, O'Riordan JI, Plant GT, Miller DH: Detection of ventricular enlargement in patients at the earliest clinical stage of MS.
Agosta F, Rovaris M, Pagani E, Sormani MP, Comi G, Filippi M: Magnetization transfer MRI metrics predict the accumulation of disability 8 years later in patients with multiple sclerosis.
Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ: Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration.
Brink BP, Veerhuis R, Breij EC, van der Valk P, Dijkstra CD, Bo L: The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions.
Geurts JJ, Barkhof F: Grey matter pathology in multiple sclerosis.
Calabrese M, Bernardi V, Atzori M, Mattisi I, Favaretto A, Rinaldi F, Perini P, Gallo P: Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing-remitting multiple sclerosis.
Zivadinov R, Locatelli L, Cookfair D, Srinivasaraghavan B, Bertolotto A, Ukmar M, Bratina A, Maggiore C, Bosco A, Grop A, et al.: Interferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy.
Tur C, Khaleeli Z, Ciccarelli O, Altmann DR, Cercignani M, Miller DH, Thompson AJ: Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS.
Pre-publication history
The pre-publication history for this paper can be accessed here:


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Press release from GlobeNewswire (a Nasdaq OMX company)
Zynga Announces Partial Release of Lock-Up Agreements With Certain Officers and Directors in Connection With Proposed Secondary Offering
Monday, March 26, 2012
Zynga Announces Partial Release of Lock-Up Agreements With Certain Officers and Directors in Connection With Proposed Secondary Offering14:00 EDT Monday, March 26, 2012SAN FRANCISCO, March 26, 2012 (GLOBE NEWSWIRE) -- Zynga Inc. (Nasdaq:ZNGA), the world's leading provider of social game services, announced today that Morgan Stanley & Co. LLC and Goldman, Sachs & Co., the joint bookrunning managers and representatives of the underwriters for the Company's initial public offering in December 2011, have consented to the release of lock-up restrictions with respect to certain shares of the Company's Class A common stock held by certain officers and directors of the Company to facilitate sales by such officers and directors in connection with the Company's recently-announced secondary offering. The release will take effect concurrently with the secondary offering, and the shares may be sold only in connection with such offering. As previously announced, on March 14, 2012, the Company filed a registration statement with the U.S. Securities and Exchange Commission (the "SEC") for certain stockholders of Zynga Inc. to offer shares of Class A common stock. The principal purposes of the offering are to facilitate an orderly distribution of shares and increase the company's public float. Zynga will not receive any proceeds from the sale of the shares. Morgan Stanley & Co. LLC and Goldman, Sachs & Co. are the joint bookrunning managers and representatives of the underwriters for the offering. BofA Merrill Lynch, Barclays Capital Inc. and J.P. Morgan Securities LLC are also joint bookrunning managers, and Allen & Company LLC is a senior co-manager for the offering. The offering will be made only by means of a prospectus. A copy of the prospectus when available may be obtained from the offices of Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014, or by email at email@example.com, or from the offices of Goldman, Sachs & Co., Attention: Prospectus Department, 200 West Street, New York, New York 10282, or by e-mail at email@example.com. A registration statement relating to the securities to be sold in the offering has been filed with the SEC, but has not yet become effective. These securities may not be sold nor may offers to buy be accepted prior to the time the registration statement becomes effective. The registration statement on Form S-1 may be accessed through the SEC's website at edgar.sec.gov.This press release does not constitute an offer to sell or the solicitation of an offer to buy any of the shares of Class A common stock nor does it constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale is unlawful. The Zynga Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=11743CONTACT: Investors - Mike Gupta 415-339-5266 firstname.lastname@example.com Press - Dani Dudeck 415-503-0303 email@example.com

subset: commoncrawl


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Dirty Girl 5K Mud Run - Twin Cities - 8/1/2015
- Sports & Fitness
- 28186 Kettle River Blvd. North, Wyoming, MN, 55092
Lean 101, September 16, 2013
Minnesota Office of Continuous Improvement
Monday, September 16, 2013 from 9:00 AM to 4:00 PM (CDT)
Lean 101 is a one-day training event that introduces public sector employees to the Lean process improvement methodology. Participants learn about the basic components of Lean, including
By the end of training, participants will begin thinking in terms of continuously improving processes within their agencies with Lean tools.
Location Details Parking is available in front of the building on 12th Street, in Lot H located west of the building, and Lot K located east of the building. Parking paystations in Lot H and Lot K accept cash, coins and credit/debit cards at an hourly rate of $1.50 and a daily rate of $6.00. Cafeterias are available in the adjacent Transportation Building and Centennial Office Building. View location map.
The Minnesota Continuous Improvement Office (MNCI) is a coordinated initiative for improving organizational performance and results in Minnesota state government.
MNCI has a simple goal of helping state government work better for its customers and employees using time-tested continuous improvement methodologies, including Lean and Six Sigma tools and philosophies.
These training courses are available to only public sector employees, including state, federal and local governments.
As of July 2015, MNCI's training registration will be transitioning from Eventbrite to the State of Minnesota's Enterprise Learning Management system. More information will be available in late May 2015.
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Fun ways to show your American pride on the Fourth
How to play hard to get without coming off snooty
This San Francisco high school plans to offer a LGBT course
Join the rebellion with these new Mockingjay - Part 2 posters
Your love horoscope this week is *major*
DIY jewelry storage for the traveling fashionista
9 times Taylor Swift gave us major hair envy
Super easy & healthy snacks to take to the pool
Have you ever been bullied? Share your story to help other girls!
GL + Disney take a look at the Teen Beach 2 premiere
More Friends = More Fun
GL Tweets !
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"HEAVY CROSS" FEATURED AS iTUNES SINGLE OF THE WEEKGossip
announce U.S. headlining tour in support of their new album Music For
Men. The tour kicks off in Washington, DC at 9:30 Club on October 7 and
runs through October 30 at Vino's in Little Rock, AR (see below for
full itinerary). Produced by multi Grammy Award winner Rick Rubin,
Music For Men is in stores on Tuesday October 6, 2009. Music For Men
has the UK press raving. Clash called it "Wild, sexy and
scintillating, 'Music For Men' is the most euphoric thing you'll hear
this year." Guardian exclaimed "Music for Men is a raised fist of a
record. This record is bigger and better than anything they've done
"Heavy Cross," the first single from Music For Men, will be featured this week as iTunes free Single of the Week (beginning today). Entertainment Weekly recently declared the single as "the triumphant return of the cult blues-punk trio." "Heavy Cross," draws you in with Ditto's vulnerable murmurs over a pulsing beat that crescendos into an explosive mix of dance and punk rock anchored by her thunderous wail. "Her voice walks a thin line between tenderness and violence, so that the overall effect strikes one like a ballerina wielding a chainsaw," was how The Observer recently described Ditto's vocal prowess. Gossip have toured extensively over the past couple years, covering the major festival circuits in North America, Europe, Australia and Japan. The band's live show has garnered critical acclaim and has cemented Gossip's reputation as one of the most exciting and relevant must-see live bands. NME raved "The greatest punk rock'n'roll disco soul band on the planet. Gossip are mind-blowing. Everyone needs to hear this band and dance like there's no tomorrow." Gossip are Beth Ditto (vocals), Brace Paine (guitar, bass, keyboards) and Hannah Billie (drums). Gossip U.S. tour dates...
These are my comments.
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Stonehenge, Windsor Castle and Bath Day Trip from London
Read what other Viator.com travelers think about the Stonehenge, Windsor Castle and Bath Day Trip from London. What they loved, what they liked and what they think could be improved, it's all here to help you make the most of your next trip.
Click here for tour details, schedule and pricing
This tour was amazing!
Very interesting, on time, relaxed - and a great guide!
Great tour!
It was wonderful and the tour guide and driver were great!The only blemish was on Viator! I needed to reschedule the trip and wrote Viator. They wrote back saying they would get back to me in 12-24 hours. I changed trip myself and then viator wrote back while I was on tour saying they couldn't help!
A long day but very enjoyable tour. The guide was very knowledgeable and had the right combination of talking and providing information with some time to rest while on the coach. There was some confusion with times at the stone henge so perhaps providing a written notice of time to return to the coach would be good as quite a few people got the time wrong and delayed the departure.
Perfect day. Long day but exactly how we like it and a lot of value for your money! Could have used more time at Windsor Castle, could have spent all day there! They really have the schedule down right to get through everything. Will definitely use them again on our next trip. Highly recommend!
This was a great tour and we saw so much in one day. All 3 places were so interesting and our tour guide Chrissy was wonderful.
The tour was one of the best I have been on! The pickup was easy and the staff was very friendly. Our tour guide was very knowledgeable and was good and providing specific directions and logistics throughout. I really enjoyed how even though it was a big group most places were audio tour and you could go at your own pace. Since I was traveling alone it was nice to move a bit quicker than the rest of the group. I absolutely loved being able to go to Hampton Court Palace since Windsor Castle happened to be closed the day we went. Bath and Stonehenge were beautiful! I would definitely recommend this trip to anyone. It seems like a long day but it goes by really fast! I thought we had just the right amount of time at each destination. Thank you Viator!
This was excellent! Kevin was our tour guide and he was professional and humorous. The history was relevant. Thoroughly enjoyed it!
This tour was wonderful. We had a great tour guide. Each stop is pretty quick so don't expect too much. It was great we saw a lot in one day.
A fabulous day! Loved all three visits, worth doing them all. Holly our guide was most knowledgable and so very entertaining all day long. Bus driver Michael Angelo was very thoughtful and kind too. A lovely safe, most interesting and fun day. Thanks Holly and Michael Angelo!
This was a great tour - our tour guide was EMILY! LOVED HER! She was one of the best tour guides I have ever had. She was very knowledgable, funny, super sweet, and just down to earth. She made the tour THAT much better! I only wish we had more time at windsor castle. I would do this tour again and again and I would also recommend that everyone takes this tour and cross your fingers that you get Emily as your tour guide!
This tour was fast paced but we got to be amazed by 3 important sites. Driver was skillful, bus was clean, guide was informative and helpful. I would do a Sima tour again.
This tour was amazing!
Tour guide did an excellent job.
Excellent time management and informative tour.
I really enjoyed this tour. The guide was really good. The coach and the scenery was great! Thanks!
Was a good day full of lots of information.
When you only have a day to pack in a lot of sights, this was a great way to do it. Our tour guide was excellent, keeping us informed and entertained without being overbearing. The pace worked out well, although it would have been nice to have more time to explore the city of Bath. Definitely worth the money.
Great value and all that was promised was delivered. Charlotte, the tour guide on the day, was very efficient and knowledgeable as she provided useful commentary. I would recommend this tour company to others.
Wonderful tour. Great tour guide in Emily and driver Craig. Very informative. A big day. We were cared for in every way and encouraged to ask for help if we needed anything.
It all ran very smoothly. Emily made sure of that. Craig was a great driver. Both were very relaxed and friendky. A great feel
Great tour. Emily was a perfect guide. Well worth the day.
It was a supper pretty tip, that I will never forget. I enjoy lots and had a new and exciting trip.
Value for money, visiting Windsor Castle and two world heritag sites.
I loved this tour! Covered a lot of ground in a short time - which is ideal if you don't have much time in London. The guide, Emily, was outgoing, informative, and engaging. The tour guide is really what can make or break a tour - she was fantastic!
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I have an autotools project. I wish to exclude some files from the project, if the user configures so during build. For example, if the build is configured with --no-gui , the files related to GUI are not to be included in the build.
What is the standard macro for such a flag in autoconf? Something that could be configured with like --disable-gui?
How to establish the link between this configure option and automake input files?
I have Calcote's introductory book Autotools here. If you can give pointers as to the macros involved, I can look it up in the book or the net.
Thank you,


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IMDb Picks: July
Visit our IMDb Picks section to see our recommendations of movies and TV shows coming out in July, which includes Minions, the third season of Showtime's "Ray Donovan", Marvel's Ant-Man, Amy Schumer's Trainwreck, and many more.
Latest News
Let the fireworks begin — or that's the hope. Terminator: Genisys and R-rated comedy Magic Mike XXL both began rolling out in North America Tuesday night before opening everywhere Wednesday in advance of the Fourth of July weekend. Magic Mike XXL, the sequel to Steven Soderbergh's sleeper hit, ... See more »
IMDb Snapshot - Latest Photos and Galleries
Exclusive Photos: Learning to Drive
As her marriage dissolves, a Manhattan writer (Patricia Clarkson) takes driving lessons from a Sikh instructor (Sir Ben Kingsley) with marriage troubles of his own. Together they find the courage to get back on the road and the strength to take the wheel.
TV Spotlight: "Killjoys"
This new Syfy series is set on the Quad, a planetary system on the brink of an interplanetary class war, where a trio of bounty hunters attempt to remain impartial as they chase deadly warrants.
New Movies on Amazon Instant Video
Hits such as Home, Ex Machina, and The Longest Ride are available on Amazon Instant Video. There's also a great selection of indie movies, including Big Game.


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Bought for a present, they love it. Healthy ideas for a nice change in usual dinner plans.Published 7 months ago by JoJo
I was very pleased with the easy to make and easy to follow recipesPublished 11 months ago by Peter B. Gaunce
Takash's Noodles has clearly written recipes that even this novice can understand! And the results are just
fabulous.... Read more
This book has great recipes and photos. Most of the ingredients are easy to find in a decent grocery store... lots of starting points to build from.Published 19 months ago by Joshua Kuensting


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over 3 years ago
Hey stranger.Imma' Smiler and Belieber. Miley Cyrus means alot to me. I really adore her. She's beautiful and a great rolemodel. Words can't describe her!<3
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Bwahahaha!! Short it anywhere now. Told ya. Patience pays shorts waiting on AFLOP. This junk can't hold $20. It's not but manipulated pump-n-dump junk.
It's guaranteed AFLOP. No one with a brain going anywhere near the over-priced, manipulated ponzi markets anymore.
Bwahahaha!! AFLOP!!!
AFLOP is rocky. Bwahahaha!! Just keep shorting until the axx clowns are muzzled with a 25% drop. Bwahahaha!! AFLOP is nothing but a pump n dump garbage stock. Fools be warned.
Patience always pays. Just keep shorting this junk every $1 past a certain level...and turn it off. Wake up one day and you're up 50%...but only worry th AFLOP! Bwahahaha!!
AFLOP pumped to dump again. No one buys this junk up here. Short it and wait. Bwahahaha! 100% predictable.
Bwahahaha! It's already falling. AFLOP never holds gains. Short more. 2% in a day just too easy.
Truly, it's 100% predictable. Meanwhile the board lackies continue to come on and try to hype this garbage when it pumps to dump. They're NOWHERE to be found when it collapses 25#$%$! Bwhahahahahaha!! I'm here all the time.
Bwahahahahahaa!! AFLOP!!
Bwahahhahaahhaaha!! Short this junk. Any buyer stupid enough to buy this junk stock up here just got hoodwinked!
Bwahahaha!! That's AFLOP! Nothing has changed with this pump and dump junk. Even the multi-id pumpers have fled again...too embarrassed to peddle and hype this diluted ponzi garbage.
Now that Zack's recommends it. Bwahahaha!!!!
Bwahahaha!!! Making money off AFLOP pumps to dump...never been so easy to make so much money.
Recommends sell low for big losses and buy high to do it again! Bwahahaha!!
Only the BFG calls AFLOP.
Up nearly $2/share now on ORIG..DRYS is another story. Still green but lightly...
Avoid it at any level.
Meanwhile, ORIG is on a tear! Only thing saving me from losing money.
I warned you suckas...meanwhile us smart folks rake in profit from your foolhardy ways. We appreciate the business, baggies. Couldn't do it without these pumps to dump...that's for sure.
Oh my...there's another bear in here that truly gets it! I remember when this junk was $43! All the same pumptards like lafeet were hyping this junk. I can't tell you home much money this knuckleheads LOST if they truly own/owned this trash. But I can tell you it's been the most single profitable ticker short in my lifetime (so far). And it just keeps on giving! So glad this r-split enabled me to start pounding it again. Simply, it was like a guaranteed bonanza when this turd announced the r-split. It's almost like seeing the dealer's hand in Vegas at the big bets table only everyday. I guarantee this company and its stock...days are numbered.
Yep, arch, if you had any profit in this turd [long], suck it right out of those manipulating this junk. Just like DRYS, any tade I got that makes, $.10+, I took it. Unfortunately, as this slithers under $.70 I'm sliding with it with little range to price protection trading. I think we'll get one get out of jail opportunity, but like Charter Comms, might have to dump it all. I'm not so excited for its near-term prospects. Hey, even the BFG has to lose one or two now and again...which is why I dislike long anything anymore. Short...I never seem to lose...at least not for long. Look at this junk trying to squeeze me again. Well, some owns a lot of shares $10+ on down because I sold it to them. Sold them even more today. Anything above $6, I'll keep selling. The equity of AMSC is worthless.


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Select Local Merchants
Sitan GymRead MoreWe can help you get into the best shape of your life. You will get a great cardiovascular and muscular workout while learning an effective and practical martial art, Muay Thai Kickboxing. We also offers children classes. Your child will get a great workout and learn self-defense while having a great time with their peers.3029 N Alma School RdChandler, AZ US
Jay Pages Jiu-Jitsu and MMARead MoreIf his belt collection is any indication, Jay Pages knows martial arts inside and out. There are three second-degree black belts in there—for Brazilian jiu-jitsu, Japanese jiu-jitsu, and submission arts wrestling—plus a second-degree black belt in judo. At his eponymous martial-arts studio, students learn Brazilian jiu-jitsu, MMA, kickboxing, and judo from instructors with similar black-belt-level expertise. The classes prevent workout boredom by emphasizing strategy, teaching the chess-like foresight required to win a fight as well as the calorie-torching moves. Furthermore, the classes are structured around clear expectations, ensuring students don't get confused about how to progress and end up buying a black leather belt at the store.114 S Southgate DrChandler, AZ US
Phoenix Quest Center for Martial ArtsRead MorePhoenix Quest Center for Martial Arts aims to provide "adventure-based leadership development through martial-arts training." The center teaches numerous courses in To-Shin Do, from children's classes to leadership training and adult self-defense. All of the classes work to help pupils make smart decisions for both their minds and bodies.3016 N Dobson RdChandler, AZ US
Phoenix Combat AcademyRead MoreAuthentic Muay Thai kickboxing with 3 time worls boxing and Muay Thai Champion, Sunshine Fettkether.114 S Southgate DrChandler, AZ US


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- Publisher: Tree Men Games
- Release Date: Aug 14, 2014
- Summary: You against the chasers. No Escape. How long would you last? See if you can make it to Top 10 on online leaderboards.
- Genre(s): General
- Cheats: On GameFAQs
- More Details and Credits »
Score distribution:
Positive: 7 out of 8
Mixed: 1 out of 8
Negative: 0 out of 8
Mar 18, 2015Pako is an action-packed racing game that is short on a story, but compensates it very well with fast-paced game mechanics. Once you start, it's hard to let go. That's always a good sign. [Feb 2015]
Aug 14, 2014With a great art style, exciting music, and fun, simple gameplay, PAKO is the most fun you'll have crashing a car.
Aug 15, 2014Pako – Car Chase Simulator is an entertaining arcade challenge that is a should buy for some intense enjoyment.
Aug 20, 2014Pako is a unique and exciting car chase simulator that you'll pick up and play and forget to put down until you're proficient. Yes, it can be hard to get the hang of, and there simply isn't much to it, but you'd be hard-pressed to find a more addictive game out there right now -- of course, beyond the likes of Timberman.
Aug 22, 2014It's certainly not the deepest game, even in its own genre. However, I have no problem offering a recommendation for what it offers.
Aug 19, 2014One never knows where the road will take us, but for now I'm really enjoying the ride Pako has to offer.
Aug 14, 2014A short, sharp, angry blast of arcade racing, Pako is challenging enough to keep you coming back time and time again.


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Emogene deGrasse Model
Remington JayModel Male Wilmington, North Carolina, US
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Emogene deGrasse Model
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Thursday, July 1, 2010 in 3,169 theaters
On Blu-ray & DVD
Tuesday, November 16, 2010
Released; Now Available Buy or Rent Now
more cast & crew
MPAA Rating
PG for fantasy action violence.
1 hour, 34 minutes
Storylines 2 view all
Air, Water, Earth, Fire. Four nations tied by destiny when the Fire Nation launches a brutal war against the others. A century has passed with no hope in sight to change the path of this destruction. Caught between combat and courage, Aang (Noah Ringer) discovers he is the lone Avatar with the power to manipulate all four elements. Aang teams with Katara (Nicola Peltz), a Waterbender, and her brother, Sokka (Jackson Rathbone), to restore balance to their war-torn world.
Additional Notes
- Based on the hugely successful Nickelodeon animated TV series, the live-action feature film "The Last Airbender" is the opening chapter in Aang's struggle to survive. Filming began in Philadelphia in May 2009. The LA Times reported that in addition to $150 million production costs, Paramount allotted a $130 million marketing budget.
More The Last Airbender Movies 2
Related Links
- Internet Movie Database (IMDb)
- The Last Airbender Official Site
- Like The Last Airbender on Facebook
- Buy The Last Airbender tickets and view showtimes
- Search The Last Airbender on Amazon


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Narrow your search
"Siri, play the top song from 1982." Apple Music's silliest element sets the new $10 subscription service apart from the pack -- but will it get you to pay?
Also known as the LG G4 Stylus, the G Stylo features a 5.7-inch display, Android 5.1, and a stylus stored inside the phone.
With the iPhone 6 and 6 Plus in the rear-view mirror now, it's time to look ahead and put in our upgrade requests for the next iPhone, whether it's called the iPhone 6S or iPhone 7.
CNET's Dan Graziano shows you how to get started with Apple's new streaming music service.
Check out the free games of July 2015 available on PlayStation Plus and Xbox Live's Games with Gold services.
The messaging platform previously only available in select parts of the US, but is now available to anyone chatting on the service.
Here is how Apple Music compares and contrasts to Spotify, one of the biggest streaming services on the market.
"We can't do everything, unfortunately."
The new features sound cool, but bugs still abound in each new mobile preview release, and Microsoft has to squash them all in time for the final release later this year.
The newest batch Hot Toys available from Sideshow bring us lifelike versions of Marty McFly, Rocket and Groot from Guardians of the Galaxy, Captain America from Avengers: Age of Ultron and a version of Batman directly based on the game Arkham City.


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Long Day's Journey Into Night: Second Edition (Paperback)
Eugene O'Neill's autobiographical play "Long Day's Journey into Night" is regarded as his finest work. First published by Yale University Press in 1956, it won the Pulitzer Prize in 1957 and has sold more than one million copies. This edition includes a new foreword by Harold Bloom, and coincides with a new production of the play starring Brian Dennehy, opening in Chicago and in New York in 2002.
About the Author
O'Neill won the Nobel Prize in literature in 1936.
The Sterling Professor of Humanities at Yale University, Harold Bloom (b. 1930) has been hailed as one of our greatest living literary critics (Los Angeles Times).


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Neill Blomkamp's 'Chappie' Poster Is at Comic-Con
Posted on Tuesday, July 22nd, 2014 by Germain Lussier
Neill Blomkamp's next film, Chappie, doesn't have a panel at San Diego Comic-Con, but if this year is proving anything, it's that panels aren't the only way to raise awareness for a project. Sometimes something as simple as an evocative poster will do the trick. That's exactly what Sony used in the case of Chappie, which stars Hugh Jackman, Sigourney Weaver and Sharlto Copley. Check out the first Chappie poster below. Read More »


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cute cats, but really playful and they love to rearrange the house!
By the way, here is something useful to check for cats: Click here.
Best Website to Watch Movies Online
A blog with a lot of funny stuff things, funny images, funny jokes, funny clips, funny pictures. Have fun is the key to be happy!


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Tortellini Primavera
Fast and filling, this dish tosses cheese tortellini together with mixed veggies and creamy Alfredo sauce. Mix things up by adding basil and diced tomato, or try vodka sauce and Parmesan instead.
Total Time:
Level: Moderate
Serves: 4
Advertisement - Continue Reading Below
- 1 package refrigerated Three Cheese Tortellini
- 1 bag frozen Sugar Snap Stir-Fry
- 1 jar creamy Alfredo sauce
- Bring a large pot of water to a boil. Add tortellini; cook as package directs, adding vegetables 2 minutes before pasta will be done. Cook until tortellini and vegetables are tender. Drain in a colander.
- Pour Alfredo sauce into pasta pot; cook over low heat until hot. Remove from heat; add pasta and vegetables and toss to mix and coat.
- Serving Idea: Stir 1⁄2 cup each slivered basil leaves and diced tomatoes into finished dish.
- Different Takes: Instead of Alfredo sauce, use vodka sauce and add some grated Parmesan cheese. Substitute mini ravioli for the tortellini.
What do you think?
The 17 Unavaoidable Stages of Eating a Slice of Watermelon
Accidentally eaten black seeds: swallow or spit?
Man Tries to Slice a Watermelon with a Sword, Fails Miserably
You HAVE to watch the video until the end.
7 Ice Cream Spritzers For Summer
They're like ice cream sodas, only so. much. better.
More From Food + Recipes


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Businesses looking for an eco-friendly host for their large events can now look to Montreal after the city was certified by iCompli Sustainability according to ASTM-APEX (Accepted Practices Exchange) standards.
SAINT-LAURENT, QC, June 18, 2015 /CNW Telbec/ - Saint-Laurent Mayor Alan DeSousa and Braulio Ferreira de Souza Dias, Executive Secretary of the Secretariat of the Convention on Biological Diversity, signed a letter of agreement today to promote their common vision on urban biodiversity.
Ecologists have warned that Melbourne is at risk of losing more than half its native plant species over the next century, with grasslands in Melbourne's west most vulnerable to the city's urban sprawl.
Using technology to make a city more sustainable works best if its inhabitants participate in planning and implementation, according to a UN report.
Berlin has the highest density of goshawk territories anywhere in the world. Since moving to the city, Amy Liptrot has delighted in the joys of watching these spectacular birds up close – in a way that would be impossible in rural areas
Over half of the world's population live in cities. They generate nearly 80% of global GDP, and use 70% of energy, according to the New Climate Economy report.
To survive on this planet at the numbers we have amassed, cities must more efficiently support their human habitants, especially with persistent constraints on water, land, and food.
My attire this morning: long johns under jeans, two layers of wool socks, heavy hiking boots, a turtleneck, two scarves, gloves, a fleece, a down parka and a knitted hat. I'm in the most populous city in the country, it's the coldest day of the year, and we're off to track coyotes.
Thirty new insect species of the fly family Phoridae have been discovered in the LA region of California.
Perching on the side of an old power station chimney with St Paul's Cathedral to the north and the Shard, Europe's tallest building, to the east is not where you might expect to glimpse the world's fastest bird. Yet Tate Modern, and London landmarks including Battersea Power Station and the Hous ...
It is Montreal and the year is 1896. The city, with its half a million citizens, is alive and vibrant and enjoying one of its greatest periods of growth.
Cities around the world are likely to suffer more heatwaves in the future, a study has found, leading to greater need for planning regulation and urban cooling.
Native bees in San Francisco provide adequate pollination to crop plants such as tomato plants, new research shows.
NEW DELHI: Global Environment Facility (GEF) that supports UN objectives on protecting environment and addressing climate change concerns, has agreed to undertake pilot projects in four Indian cities for promoting green practices in urban areas.
Critics say it will destroy one of the island's few remaining untouched green spaces, block a natural green corridor used by dozens of species and bring 10,000 more cars to a region plagued by traffic congestion
Perth is not a big part of the national consciousness, although its growth has sparked some interest. The latest Australian Bureau of Statistics projections are remarkable—the population will reach three million by the early 2020s, surpass Brisbane later that decade and hit five million by 2050, ...
BUENOS AIRES, Feb 5 2015 (IPS) - If cities have souls, the Argentine capital's is turning more and more grey. Real estate speculation, the fencing in and paving of parks, and the installation of private bars and restaurants in public squares have changed the face of the city.
European rabbits are in decline in rural areas, yet holding strong in cities. But urban living also comes with a changed lifestyle: instead of being packed into complex burrows, city rabbits seem to live a more solitary life in smaller burrows.
'Cloudburst boulevards' and innovative bowl-shaped parks are designed to protect the city from rising sea levels
Urban farming could improve food security but also increases the competition between urban and rural water needs.
Across Australia - and the world - the future of large old trees is bleak and yet large trees support many species such as birds and small mammals, says Mr Darren Le Roux, a PhD student at the ARC Centre of Excellence for Environmental Decisions (CEED) and The Australian National University.
A new project attempts to find solutions to allergies and other immune defence disorders using methods from medicine and urban design.
NEW YORK, Dec. 2 (UPI) -- For junk food-loving insects, New York City is the place to be. According to new research, urban-dwelling bugs -- millipedes, ants, spiders and cockroaches -- roaming a 150-block stretch of the Broadway/West Street corridor consume the equivalent of 60,000 hotdogs each ...
Deep in the woods at Alley Pond Park in Queens is a laboratory that looks like something out of a weather fanatic's wild imagination.
Urban environments are changing rapidly. People who live in cities are faced with risks and vulnerabilities that depend as much on socioeconomic factors, like access to health care, as they do on exposure to climate change and variability.
Researchers at the Smithsonian Migratory Bird Center have found four bird species living in the Washington, D.C., metropolitan region that survive longer than those living in rural settings.
Cities have more species diversity than you'd expect. A study of ants in Manhattan found not only a wide range of species, but also significant differences in the levels of biodiversity in different urban areas.
Planting trees and creating green space in cities is good for attracting species, but it may not be enough to ensure biodiversity in built environments, a University of Iowa study has found.
31 October 2014 – As the world's urban areas inevitably expand, growing both in size and in population, they will also need to transition into better planned and better managed environments or risk exacerbating negative trends, the United Nations warned today.
Unable to fly, nestling birds depend on their parents for both food and protection: vocal communication between parents and offspring helps young birds to determine when they should beg for food and when they should crouch in the nest to avoid a predator seeking an easy meal.
I love bees. Everyone I know loves bees. And everyone knows bees are on the decline. But could it be that cities will come to their rescue?
Brussels boasts being one of Europe's greener cities, even though many of its parks are far from inner-city residents. In response, some people have created their own pop-up parks out of vacant lots.
[NEW YORK] More than 2,000 cities have banded together in what the UN calls the largest effort by cities so far to curb their greenhouse gas emissions.
As world leaders gathered at the U.N. to talk about global warming, mayors set about actually doing something about climate change
Gujarat city on India's west coast is preparing to cope with twin disasters brought on by rapid growth and global warming
More than 8,000 hectares of rainforest are under threat as the nation builds a new $600 million capital city from scratch. Called Oyala, and also known as Djibloho, the city is expected to be completed by 2020 and house up to 200,000 people -- about an eighth of the entire population of the enti ...
Manila is known more for its gridlocked traffic jams and air pollution than for green spaces or pedestrianized walkways. Bamboo bikes could change that by curbing emissions and helping pave the way to go green.
Urban great tits have smaller black breast stripes than their rural neighbours, a study has found.
Toronto's 10 million trees are worth an estimated $7-billion or about $700 per tree and the benefits of maintaining an urban forest outweigh the costs, says a new report.
SINGAPORE, Jun 5 2014 (IPS) - With over 20,000 international participants, a triple summit wrapping up today in Singapore is generating an abundance of ideas on sustainable cities.
5 June 2014: Three events, the World Cities Summit (WCS), the Singapore International Water Week (SIWW) and the CleanEnviro Summit (CESS) 2014, have brought together over 20,000 participants in Singapore, including 30 Ministers and 130 mayors, to share experiences and technological innovations, ...
A 10% increase in green space in our cities could help to keep temperatures at present levels into the 2050s, despite climate change
Changes to UK urban areas provide habitats for mosquitoes, including species known to spread malaria and West Nile virus, a study suggests.
HUMANS are becoming ever more urban in their habits, yet it's only recently that scientists have attempted to quantify the impact of urbanisation on levels of biodiversity around the world.
5 May 2014 – The United Nations Office for Disaster Risk Reduction (UNISDR) has announced that it will partner with a California-based supplier of global geographic data to make available new technologies that can help communities and cities visualize disaster risk and take action.
Johannesburg — Cities in developing countries with quality health, housing and water drainage systems, can more easily adapt to a changing climate, says the new Intergovernmental Panel on Climate Change (IPCC) report.
Subsiding land is a bigger immediate problem for the world's coastal cities than sea level rise, say scientists.
Half the world's people live in cities – but urban environments have just a 10th of the species present in equivalent countryside habitats. Should we care and what can we do about it?
Public perception of wildlife tends to be tied to natural habitats such as forests, ocean and other wild settings.
Smart choices by cities such as Miami in planning and investment could hold key to cutting emissions, IPCC draft says


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i wanted to re-edit this photo set and make these photos look more the way i originally wanted them to look when i first posted them last year. they're much less saturated with purples/blues and more realistic to how that day actually looked in person. i also took out a few photos i didn't like much anymore. the original photo set blew up so much that there's no way this one will get anywhere close to that much attention, but i wanted to re-post them anyway :-)
andorra, pa


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We kicked the season off right with a fresh setup in Arctic Blast and some legit features over at Hidden Valley. Park Team jumped right back into things and turned up the heat. Featuring Jordan Soohy, Kevin Kobasa, Josh Zerkel, Jackie Flanagan, Clint Cooper, Trevor Eichelberger, Mike Zandron, Cooper Thomas and AJ Lawson
Filmed and edited by Ian Macy
"Sunder" by Hibou
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