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Depressed mood is a frequent co-morbidity of dementia suggesting that they might share a common neuropathological substrate. Gray matter (GM) atrophy and white matter lesions (WML) have been described in both conditions. Our aims were to determine the relationship of GM and WML with cognition and depressed mood in the same population. Structural brain images were obtained from 42 controls, 20 Alzheimer's disease (AD) patients and 32 subjects with cognitive impairment/dementia due to subcortical cerebrovascular disease (vascCIND/IVD) and segmented to obtain lobar GM, white matter and WML volumes. Lobar WML had a negative effect on GM in all lobes in controls, on frontal, parietal and occipital GM in AD and on frontal GM in vascCIND/IVD. Frontal, temporal and hippocampal GM were associated with cognitive functions and frontal WML load with depressed mood. Cognitive function is associated with GM atrophy and depressed mood is associated with frontal WML. This indicates that although both often occur together depressed mood and cognitive impairment are caused by different pathological correlates.
Depression and depressed mood are a common co-morbidity of dementia as about 20–25% of the patients diagnosed with Alzheimer's disease (AD) (Payne et al., 1998) and 20–50% of the patients diagnosed with vascular dementia (IVD) (Simpson et al., 1999) suffer from depressed mood or even meet the criteria for major depression. However, late life depression is also a well known risk factor for the development of cognitive impairment and dementia (Mondrego and Fernandes, 2004; Thomas and O'Brien, 2008). These observations suggest that late life depression and dementia might share common underlying functional and/or structural correlates.
Two potential candidates for such a common correlate are suggested by the literature: white matter lesions (WML) and gray matter atrophy. Several neuroimaging studies for example have demonstrated an association between an increased WML load and depression in cognitively intact elderly subjects but also in patients suffering from AD or other types of dementia (Lopez et al., 1997; Thomas et al., 2002; Heiden et al., 2005; Minett et al. 2005; Teodorczuk et al., 2007; Lee et al., 2008). Furthermore, it has been repeatedly shown that impaired cognitive performance in non-demented elderly subjects is related to increased WML load (van der Flier et al., 2005, Burton et al., 2008) and that concomitant cerebrovascular disease is associated with more pronounced cognitive impairment in AD (Jellinger, 2005). The exact pathomechanism, by which WML affect cognition and mood is unknown. The commonly proposed mechanism however is deafferentation, i.e., that subcortical pathways connecting cortical brain regions crucially involved in the control of mood and cognitive function (Taylor et al., 2006) are interrupted by WML which then results in neuronal dysfunction and eventually even neuron loss in these cortical regions (Wakayama et al., 1989).
There are also good arguments that cortical gray matter is the common substrate for cognition and mood. Several neuroimaging studies in cognitively normal elderly found depression to be associated with circumscribed frontal cortical GM losses (Ballmaier et al., 2004; Lind et al., 2006; Rainer et al., 2006; Andreascu et al., 2007; Lavretsky et al., 2007). In addition to this, studies assessing the influence of WML load as well as GM atrophy on cognitive function in cognitively intact and impaired subjects, found cognitive impairment to be correlated with GM atrophy but not with WML load or other manifestations of cerebrovascular disease, e.g. lacunes (Mungas et al., 2002). These findings suggest that processes directly affecting cortical regions involved in cognition and mood control rather than their disconnection due to remote WML causes cognitive impairment and mood disturbances.
One of the reasons for these discrepant findings could be that the majority of these studies tested either the influence of WML load or GM atrophy on cognition or the influence of WML load or GM atrophy on depression. Only few studies have investigated the effects of both WML and GM atrophy on both cognition and depression in the same population (Mungas et al., 2005; Taylor et al., 2007). Therefore, the overall goal of this study was to further explore the relationship between WML load and GM atrophy and their association with depressed mood and cognition in a population consisting of cognitively intact elderly subjects and patients suffering from cognitive impairment or dementia due to cerebrovascular disease or AD. Specifically, we pursued the following aims: 1. To determine the characteristic atrophy patterns and the relationship between lobar GM volume loss and lobar WML load in the total study population and in each subgroup. We hypothesized that lobar WML load would be significantly negatively correlated with lobar gray matter in all lobes in controls but that the relationship between lobar WML load and gray matter would be mitigated by the disease in AD (particularly in the temporal and parietal lobe) and subjects with cognitive impairment due cerebrovascular disease (particularly in lobes with high WML load). 2. To determine the relationship between lobar GM atrophy and lobar WML load and cognitive functioning (global cognition, executive function, verbal and non-verbal memory. Based on previous studies (Mungas et al., 2002) we hypothesized that cognitive function would be correlated with GM volume, particularly frontal and temporal GM volumes, but not with WML. 3. To determine the relationship between presence of depressed mood (presence of major depression or depressive symptoms, e.g. apathy, anergia, anhedonia, depressed mood) and lobar gray matter and WML load.
The study population consisted of 94 subjects selected (based on image quality and completeness of clinical and neuropsychological information at the time of the MRI) from study participants of a large multi-center project conducted by three academic dementia centers (University of California Davis, University of California San Francisco and University of Southern California) which studies the contributions of subcortical vascular disease and Alzheimer's disease to cognitive impairment and dementia. The study had been reviewed and approved by the institutional review boards of all three study sites and written informed consent had been obtained from the study participants or their legal representatives.
Forty-two of the study participants were elderly cognitively intact control subjects, 21 were cognitively impaired due to subcortical cerebrovascular disease (vascCIND) and 31 were demented (11 were diagnosed with subcortical cerebrovascular or mixed dementia (IVD) based on the California Alzheimer's Disease Diagnostic and Treatment Center criteria (ADDTC) for ischemic vascular dementia and 20 were diagnosed with AD according to the diagnostic criteria of the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA)). All participants received a comprehensive clinical neurological and psychiatric evaluation, an extensive neuropsychological battery and structural MRI exams. (cf. Table 1 for characteristics of study population).
All participants received a standardized battery of neuropsychological tests within six months of the MRI. The Clinical Dementia Rating Scale and the Mini Mental State Examination were used as standard clinical assessment of global cognitive function. For the analysis of domain specific functions, the following four composite scores were calculated using Item response theory methods: global cognition (GlobalCog), verbal (vMem) and non verbal (nvMem) memory function and executive function (Exec). The procedures and validation of these scores have been described in detail elsewhere (Mungas et al., 2002; Mungas et al., 2003; Mungas et al., 2005; Reed et al., 2007). To summarize briefly: The GlobalCog score was based on total recall on trials 1 and 2 on the Word List Learning Test of the Memory Assessment Scales, the performance in the Digit Span forward and backward test from the Wechsler Memory Scale and the letter fluency test (letter A from "FAS" test and the animal category fluency test). The Exec score was calculated based on the Initiation-Perseveration subscale from the Mattis Dementia Rating Scale, the FAS test, the Digit Span backward and the visual memory span backward test. The vMem score was based on the performance in The Word List Learning Test of the Memory Assessment Scales and the nvMem score on subtests from the Biber serial design learning test.
Behavioral ratings were derived from clinician ratings using the Psychiatric Evaluation section of the Minimum Uniform Dataset of the California Alzheimer's Disease Centers Program. The final assessment of the presence of depressive symptoms was based on the patient and caregiver report, and direct clinical examination (Lavretsky et al., 2008) which were obtained at the same time as the neuropsychological evaluation. For the purpose of this study, a subject was characterized as suffering from depressed mood if this person had either been diagnosed with major depression (according to the DSM-IV criteria) or if one or several of the following depressive symptoms were present during this examination: anhedonia, apathy, anergia, depressed mood not fulfilling the DSM criteria for major depression. Absence or presence of depressed mood was expressed with one dummy variable: yes, if the subject displayed any or several depressive symptoms or was clinically depressed; no, if the subject displayed none of the depressive symptoms and was also not clinically depressed. No attempt was made to differentiate between the different depressive symptoms or to account for the severity of these symptoms, for the fact that some subjects displayed more than one symptom or for lifetime history of depression. Subjects who diagnosed with other psychiatric disorders than depression or depressed mood during this examination were excluded from the study.
All subjects were studied on the same 1.5 T Magnetom Vision MR system (Siemens, Inc Iselin, NJ, U.S.A.) and the following sequences acquired. 1. Double spin-echo (DSE) TR/TE1/TE2 = 2'500/20/80 ms, 1.0×1.4 mm2 in-plane resolution, slice thickness 3 mm orientend along the AC-PC line. 2. Volumetric magnetization-prepared rapid gradient Echo (MPRAGE), TR,TE/TI = 13.5/7/300 ms; 1.0×1.0 mm2 in plane resolution, slice thickness 1.4 mm oriented along the long axis of the hippocampus.
In a first step, each subject's T2 and proton density (PD) weighted images were co-registered and re-sampled to the resolution of this subject's MPRAGE image using the Automated Image Registration software (AIR version 3.0). In the next step, the T1 image was spatially normalized to a customized T1 weighted template (derived from 64 subjects, female/male: 30/34, mean ± SD age 56.6 ± 18.6 years) (Maes et al., 1997) and the thus derived transformation parameters were also applied the co-registered T2 and PD. The normalized images were then segmented into probabilistic gray (GM) and white matter (WM), cerebral spinal fluid (CSF) and white matter lesion(WML) maps using the multi channel segmentation of Expectation Maximization Segmentation (EMS) (van Leemput et al., 1999; van Leemput et al., 2001). Customized GM, WM and CSF priors derived from the population which had been used for the generation of the T1 weighted template, were used to initiate the EMS algorithm.
An atlas based deformable registration method was used to automatically identify frontal, temporal, parietal and occipital lobes, cerebellum, subcortical gray matter (basal ganglia and thalamus) and brain stem. For this purpose the MRI of a single elderly subject was selected as a template on which these structures were manually delineated. A B-spline free form deformation algorithm driven by normalized mutual information was used to warp each individual T1 image onto this template (Studholme et al., 2003; Studholme et al., 2004). The spatial transformation parameters obtained by this process were inverted and applied to the template lobar markings to create lobar marks in subject space which were then applied to the individual tissue maps. A binary mask derived from the skull-stripped T2 image of each subject was used to ensure that subarachnoidal CSF spaces were captured in their entirety and mis-classified non-brain structures, e.g., dura, were excluded. Total lobe volume (sum of GM, WM, WML in each lobe), GM volume and WML volume were calculated for each lobe. Hippocampal volumes were determined using a commercially available semi-automated high dimensional brain warping algorithm (Medtronic Surgical Navigation Technologies, Louisville, CO). To account for different head sizes, all volumes were normalized to each subject's total intracranial volume (TIV) using the following formula: normalized volume = raw volume*1000/TIV. TIV was calculated by adding the volume of all voxels classified as CSF or brain tissue from the frontal, temporal, parietal, occipital and subcortical structures but excluded voxels classified as brain stem and cerebellum because these structures were not represented in their entirety in all subjects.
Differences of demographic variables (age, years of education, gender distribution) between groups were assessed using ANOVA for continuous, and chi-square tests for categorical variables. Normalized brain measures were grouped into the following categories: 1. lobe volumes (frontal, parietal, temporal, occipital lobe volumes) to assess effects of overall atrophy. 2. gray matter volumes (frontal, parietal, temporal, occipital, hippocampal GM). 3. lobar WML load (percentage of the lobe volume (frontal, parietal, temporal, occipital) segmented as WML, which was log transformed to achieve normal distribution (ln%WML)). Within each of these structural categories group differences were assessed with MANCOVA with adjustments for age and gender, e.g. all lobar GM volumes were entered simultaneously as dependent variables and age, gender and group were modeled as independent variables. Significant group effects in the MANCOVA were followed by individual ANOVA tests using Tukey's correction for multiple comparisons. To identify factors influencing lobar GM volume in the total study population, multiple linear regression analyses with lobar GM volume as dependent and age, gender, group, lobe volume and lobar WML load as independent variables were used. A similar but slightly modified regression analysis (gender not modeled, since there were no significant gender effects in the total population) was used to identify factors influencing lobar GM in each diagnostic group (controls, AD and IVD/vascCIND) IVD and vascCIND were combined into one group for this analysis because the IVD group was rather small.
A multi-level regression approach was used to test for associations between brain structures with cognition (linear regression) and depressed mood (logistic regression). In the first level, the contribution of demographic variables to cognition (independent variables tested: age, gender, years of education, presence/absence of depressive symptoms. Group was not included because it was intended to test for structural-cognitive correlations over the whole range of cognitive impairment represented in the study population) respectively to presence of depressed mood (independent variables tested: age, gender, group) was assessed using multiple regression analysis. The second level of the analysis consisted of a stepwise regression in which cognitive measures or presence of depressed mood were defined as dependent variables, and the measures of one structural category, e.g. lobar gray matter volumes and hippocampal volume, were entered into the model in a stepwise fashion (forward selection, probability to enter/leave 0.05). Demographic variables significantly associated with the dependent variable in the first level analysis were forced into the stepwise model as independent variables before brain measures were entered. This analysis was repeated for each structural category. The last level was a stepwise regression analysis (forward selection, probability to enter/leave 0.05) in which cognitive measures or presence of depressed mood were again entered as dependent variable and all brain measures for which significant effects had been found at the second level analyses were entered as additional independent variables. Again, demographic variables significantly associated with the dependent variable in the first level analysis were forced into the stepwise model as independent variables before brain measures were entered. All statistical analyses were done with JMP version 7.0 (2007, SAS Institute Inc.).
The MANCOVA tests using the different brain tissue categories as dependent variables revealed significant effects for "group" and the covariate "age" but not "gender" for lobe volumes (group: Wilks' lambda 0.708, F (12,225.2) = 2.62, p = 0.0028; age F(4,85) = 6.96, p <0.001), GM volumes (group: Wilks' lambda 0.433, F(15,232.3) = 5.49, p<0.0001; age: F (5,84) = 10.7, p<0.0001) and lobar WML load (group: Wilk's lambda 0.778, F(12,225.2) = 1.87, p = 0.039; age: F(4,85) = 4.37, p = 0.029). The associations with "age" were negative for lobe and GM volumes and positive for WML load. Table 2 shows the results of the post hoc tests.
Multiple linear regression analysis was used to identify brain measures associated with GM volumes (cf Table 3). As expected, there were positive correlations of lobe volume with lobar GM volumes in the total population as well as in each of the subgroups. Lobar WML loads were negatively correlated with their corresponding cortical GM volumes in controls. In the total population and in the AD subgroup frontal, parietal and occipital WML load but not temporal WML loads were negatively associated with their corresponding lobar GM volumes. In the combined IVD/vascCIND group, frontal GM was negatively correlated with frontal WML. There were no significant correlations of lobar WML load with GM of any of the other lobes.
In the multiple regression analysis all cognitive variables were negatively influenced by depressed mood, i.e., subjects with depressive symptoms had lower cognitive scores than subjects without depressive symptoms (GlobCog: p<0.0001, Exec: p = 0.017; vMem: p <0.0001; nvMem: p = 0.0001) but not by age, gender or years of education. Therefore "presence of depressed mood" was forced into the second step models. Age, although not significant in the first step analyses, was also included to account for age-related changes of brain volumes. The findings of the second level analysis are summarized in Table 4. When testing for correlations between lobar volumes with different cognitive modalities, significant effects were only found for temporal lobe volume which was positively correlated with better performance in GlobCog, vMem and nvMem but not Exec. Frontal and temporal gray matter volumes had significant positive associations with GlobCog and Exec, frontal, temporal and hippocampal GM volumes were positively correlated with vMem and nvMem. When testing for effects of lobar WML load on cognitive function, the only cognitive measure showing an association was Exec which was negatively correlated with parietal ln%WNL. In the last level analysis, all brain measures, i.e. lobe volumes, lobar GM volumes or lobar ln%WML volumes which had shown significant associations with a particular cognitive measure in the previous level were entered in a stepwise fashion into the model, to identify those structures which had the highest and statistically independent association with this function. In this analysis, temporal lobe volume and parietal ln%WML did not enter the model; performance in all four cognitive domains was solely associated with those GM volumes for which significant effects had already been found in the second level analysis (cf Table 5).
Presence of depressed mood was significantly associated with 'group' in the logistic regression analysis with depressed mood being less common in controls than in the other subgroups (p<0.0001). Neither age nor gender were significantly associated with presence of depressed mood. Based on this, "group" was forced into the model for the second level stepwise logistic regression. Again, 'age', although not significant in the first level analysis, was also forced into the model to account for age-related changes of brain volumes. The only brain measure showing a significant association with depressed mood in the second level analysis was frontal WML load (p = 0.025) with subjects suffering from depressed mood having higher frontal WML load than subjects without depressed mood (cf Table 5).
There were three major findings in this study: 1. As expected, AD and subcortical cerebrovascular disease had different patterns of GM atrophy. The subgroups also differed regarding associations between lobar WML and lobar GM. 2. GM structures but not WML determined cognitive function. 3. The presence of depressed mood was associated with an increased frontal WML load but not with GM atrophy. Taken together, these findings indicate that although they often occur together, depressed mood and cognitive impairment/dementia have different underlying pathomechanisms.
The first major finding was that the influence of lobar WML on lobar GM was different in the three groups. In controls, lobar WML load had a significant negative effect on GM in all lobes. AD was, as expected, characterized by hippocampal, frontal, parietal and temporal gray matter loss. Lobar WML load was negatively associated with frontal and parietal GM but not with temporal GM. The early stages of IVD (vascCIND) were characterized by predominantly hippocampal and occipital GM losses, and the later stages (IVD) by global GM loss Except for the frontal lobes, lobar WML load had no significant negative effect on cortical GM in vascCIND/IVD. Theoretically, there are two possible explanations for the significant negative associations between lobar WML and lobar GM observed in this study. 1. Lobar WMLs interrupt axonal connections between subcortical and cortical gray matter structures. This results in deafferentation/disconnection of functional pathways, dysfunction and eventually death of cortical and subcortical neurons and thus ultimately in GM atrophy. (Wakayama et al., 1989; O'Sullivan et al., 2001). 2. MRI-histopathological correlations have shown that MRI WML in elderly are highly correlated with histopathological manifestations of small vessel disease (Scheltens et al., 1995; Brown et al., 2002; Enzinger et al., 2007). Therefore, lobar WML could simply represent a marker of small vessel disease in a particular lobe (WM and GM) without WML directly causing GM atrophy as assumed by deafferentation/disconnection mechanism. Both mechanisms or combinations thereof are likely to be active in lobes showing a significant association between GM and WML. However, this WML/GM atrophy correlation was not found in the occipital and temporal lobes of AD and in the parietal, occipital and temporal lobes of vascCIND/IVD. This suggests that alternative and/or additional pathomechanisms causing GM atrophy are active there. In AD, neuronal degeneration due to AD related pathomechanisms and in vascCIND/IVD local cortical ischemic effects, e.g. microinfarcts (Koevari et al., 2004) or a combination of AD and local ischemic pathomechanisms in mixed dementia are likely alternative pathomechanisms. Although neuronal death due to these mechanisms also would result in axonal degeneration and thus WM pathology, the resulting WM abnormalities would be diffuse and thus not result in WML but rather in diffuse lobar WM volume loss. Taken together, these findings show that at least in this population, ischemic WML load has no uniform effect on cortical GM but that its effects are probably modulated by locally or diffusely active ischemic or non-ischemic pathomechanisms.
The second major finding was that cognitive function was determined by lobar GM volume but not by lobar WML load. This confirms the findings from previous studies from this collaborative project which found cognitive functioning to be determined by total cortical gray matter and hippocampal volume. In contrast to those studies (Mungas et al., 2001), we had lobar brain measurements and were thus able to test for associations between lobar volumes and different cognitive domains. Global cognition as measured by the GlobCog score and executive function measured by the Exec score were correlated with frontal and temporal GM volumes, while memory as measured by the vMem and nvMem scores were correlated with frontal, temporal and hippocampal GM volumes. There were no direct associations of lobar WML load with cognitive function. We cannot exclude that this finding is driven by the study population in which the subjects with the most pronounced cognitive impairment suffered from dementias characterized by prominent gray matter loss. However, it could be argued that even in this population WML had at least an indirect influence on cognition as frontal WML had a significant negative effect on frontal GM in the population as a whole and in each of the subgroups.
In contrast to other studies assessing the effects of WML on cognition (van der Flier et al., 2005; Burton et al. 2006), this study accounted for the presence of depressed mood in the statistical analysis. Because of the reported association between WML with depressed mood and cognition, it is possible that this is the reason, that we did not find an association between WML and cognitive function. Repeating this analysis without modeling for presence of depressed mood (data not shown) showed a significant negative association with parietal WML load (p = 0.03) on the Exec score in the third level analysis in addition to the positive effects for frontal and temporal GM which had also been observed when depressed mood was accounted for. None of the other cognitive domains was influenced by lobar WML. It is interesting that it was parietal WML that had a significant effect on Exec when presence of depressed mood was not accounted for and not frontal WML which was the only measure correlated with depressed mood. There is evidence that input from parietal regions (Brodmann area (BA) 7 and BA40) has modulating effects on the dorsolateral prefrontal circuit (Liotti et al., 2000; Tekin et al., 2002). Functional neuroimaging studies have shown that the dorsolateral prefrontal circuit is involved in executive function and also controls feelings of sadness. Therefore, a disruption of afferent modulating inputs on this circuit by parietal WML could be expected to impair executive function and cause symptoms associated with depression. Taken together, these findings show that the main domains of cognitive functioning are correlated with hippocampal, frontal, temporal GM volumes in this mixed population. If effects of depressed mood were controlled for, WML load was not correlated with cognitive function except for an indirect influence via its negative association with GM.
The third major finding of this study was that the presence of depressed mood was associated with increased frontal WML load. This finding supports the hypothesis that depressed mood can be caused by an interruption of pathways connecting cortical frontal regions involved in mood control (BA 9, 10, 11, 24) with subcortical structures (caudate nucleus, pallidum, thalamus) (Liotti et al., 2000;Tekin et al., 2002). In contrast to other neuroimaging studies in elderly cognitively normal subjects with depression (Lavretsky et al., 2007; Andreascu et al., 2007; Ballmaier et al., 2004; Taylor et al., 2007), we found no direct significant association between depressed mood and frontal GM volumes. There are three potential explanations for this discrepancy. 1. The previous studies concentrated on subjects diagnosed with major depression while most of the subjects in this study did not fulfill the criteria for major depression. 2. In contrast to those previous studies, our study population also included cognitively impaired and demented subjects with the latter suffering more often from depressed mood than the former. Although we tried to correct for this imbalance by including "group" in the statistical model, we cannot exclude the possibility that potential correlations of depression with frontal GM volume were overshadowed by more prominent effects of AD or cerebrovascular disease. 3. Those previous studies divided the frontal lobe into different regions of interest and found that it was primarily orbito-frontal GM loss which was associated with depressed mood. In this study, we measured frontal GM as a whole and thus might have missed circumscribed frontal GM effects. However, we found an indirect association between frontal GM and frontal WML as the latter was negatively correlated with the former in the total study population and also in each of the subgroups. This finding suggests that the interruption of subcortical pathways due to WML resulted in deafferentation and consequently frontal GM atrophy loss which could have contributed to the development of depressed mood.
This study has limitations. 1. The diagnosis was based on clinical criteria as only six patients in this series came to autopsy (confirmation of clinical diagnosis in four, two subjects diagnosed with AD were found to have mixed dementia at autopsy). Autopsy studies in large community dwelling populations have shown that mixed pathologies are very common in demented subjects (Schneider et al., 2007) and thus the attempt to subdivide our population into specific diagnostic categories and describe disease specific atrophy patterns might not reflect the reality. 2. We obtained lobar information only and were thus not able to address questions regarding laterality of cognitive functions or differences of deep and periventricular WML on gray matter and cognitive function respectively mood. As pointed out in the previous paragraph, this also prevented us from finding associations of circumscribed cortical regions with cognition or depressed mood. 3. The statistical analysis is quite complex and required several tests and a multi level analysis. Since we had a priori hypotheses for the first two issues (influence of WML on GM and relationship between cognitive function and lobar volumes) we did not apply a correction for multiple comparisons for those analyses. However, we did not have an a priori hypothesis for the third issue (relationship between depressed mood and lobar volumes) and thus a correction for multiple comparisons would have been appropriate but was not applied. It will be necessary to confirm this finding in a different, larger population. 4. The definition of "depressed mood" used in this study does not fulfill the DSM-IV criteria of "major depression". This limits the comparability of the findings of this study with other studies using the stricter DSM-IV criteria.
In conclusion, AD and subcortical IVD show different patterns of GM atrophy. Frontal WML load is associated with frontal GM volume in controls and cognitively impaired subjects. In the other lobes, the contributions of lobar WML load to GM atrophy are mediated by additional local disease specific effects. Cognitive impairment (global functioning, executive and memory function) is determined by gray matter losses in the temporal and frontal lobes while frontal WML load but not gray matter atrophy determines the presence of depressed mood. These observations suggest that although they often occur together depressed mood and cognitive impairment are caused by different pathological correlates.
This study was supported by the National Institutes of Health grant P01 AG12435 to H.C. Chui and M.W. Weiner and the Department of Veterans Administration. We also gratefully acknowledge the expertise of Mr. Derek Flenniken in database management which was essential for this study.
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None of the authors had any actual or potential conflict of interest.
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Highlighting the Western Canada High School Community
Western Canada Students Support
Safety in Schools
At the September 18, 2014 media event reception for the promotion of the Safety in Schools online program, WCHS students Clare Song, Gracia Joulie and Taylor Newel provide their personal testimonials about how workplace safety training is essential for their work experience. The risk of injury and fatality in youth workers aged 15-24 lowers dramatically with this course available at Western and 160 schools in Alberta.
Western Canada Alumni Visit
A Recent Visit from 4 Redmen Basketball alumni to Western Canada. During their visit they discussed the name change and re-lived memories of their days playing for Western Canada High School.

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Today, I'm proud of myself.
I started out with a big ol' heap 'a books two weeks ago. Normal, right? Yes, but not always do I get through that big ol' heap before I have to return them. Today is different! I finished this heap, and I found a good mix of what I liked and what I didn't even know I liked in it. As usual, I grabbed an assortment of books without reading the descriptions, because surprise. I call it the Schneider Variety Pack. My boyfriend was with me this time, and I assigned him with finding one book. Read Between the Lines was what he chose, because "the cover has a smiley face on it". He's a man of depth, that man of mine.
Read Between the Lines is interesting because it's one of those books that holds many stories in one. We start with Nathan, the school punching bag with an abusive father and a crappy home life. During PE, Nathan breaks his middle finger, which is proudly displayed for all to see. He finds empowerment in it and soon others are laughing with him, not at him. We see a variety of characters all tied together and from different walks of life, like the popular cheerleaders Grace and Claire and the timid Ms. Lindsey. We get a glimpse into their lives and see that, like usual, nothing is as it seems. A powerful resolution from Ms. Lindsey ends the book, and it's a treat to read up to the very end.
Books like these always pack a certain punch. It puts things into perspective that we really don't know what's going on with others, even if we think we have them labeled and placed into all the right categories. If you like getting attached to characters, I wouldn't go for this one–each character gets around a chapter and then kaput, they're out. However, because each is linked, it's interesting finding the points of intersection. Another fun aspect? Flipping people off is constant in this book. Either someone is doing or receiving the bird, which I liked. It's naughty and it's funny, and I've got the sense of humor of an eleven year old boy, so that's that.
Though its characters are from one singular place and the events happen in one singular day, this novel feels like much more. It did drag at some points, but the ending is worth it. I'd recommend it any day, so try it out if you feel up to it! And if you don't, go and get a bag of brownie brittle and turn on Netflix to Grace and Frankie or whatever you prefer. I promise I won't tell.


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School is back in session and so is snacking. It's often easy to grab a quick packaged snack or sugary midday treat. But by taking an extra minute to prepare a quick, painless and simple snack you'll feel better, you'll avoid the inevitable sugar crash and you'll provide your body what it needs to function more efficiently. Whether you're a student or a full-time member of the workforce, here are a few truths about snacking, from us to you:
These are just a few quick tips to help you snack better. What are you favorite go-to snacks that keep you energized and feeling good?


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Arty & Chikle are a street art duo from Mexico City that loves illustration, street art, toys and cartoons. They have been working together since 2013, but before that they were both dedicated completely to street art, illustration and design and each of them had several collaborations with brands and galleries; after been invited to participate in a collective art show in Mexico City by the end of 2012, they met for the very first time and decided to begin a brand new project fusing their styles and concepts. They consider themselves as part of the Furry Fandom (a subculture of people that love animal characters with human traits) that's why their art is full of toony zoo anthropomorphic characters. Their work is full of cute, chaotic and surreal situations where love, death, drugs and sex are their main themes. They have painted all over Mexico, Costa Rica and Brazil, and have had several gallery exhibitions in Mexico and Costa Rica; they have participated in a few Art Festivals and look forward to many more.
Tora Boy is a cute, innocent yet playful tiger who likes to travel and make new friends whenever he has the chance to. We are very happy and satisfied with him and we are sure he will have lots of fun abroad and meet lots of new friends!


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Best of Italy, September 2017
Deborah Bracci
Best value for money tour you will find!! Excellent opportunities to see, taste and explore the very best locations in Italy.
Review submitted 22 Oct 2017
Athens to Santorini, September 2017
Leanne Corrie
TO ALL AT INTREPID TRAVEL, A heart-felt thank you to INTREPID TRAVEL for taking me to incredible places and on amazing adventures on my recent ten weeks to Mediterranean countries. Greatest gratitude to Natalie Scales-Melbourne Team Leader- Travel Consultant who organised 70 days of stress free travel with all seven flights, trips and all the other arrangements and the sound advice for the days not travelling with Intrepid tours going so smoothly to make my journey an unforgettable life time experience. My five Intrepid leaders in Europe were caring, efficient and organised and the single supplement accommodation was very comfortable with some great surprises like beautiful balcony views, tastefully decorated, roof top restaurants and locations. The Intrepid trips- Explore Spain and Portugal, Rome to Amalfi, Best of Italy, Dubrovnik to Athens and Athens to Santorini were all so different and I would recommend all of these to people who like small group travel, everyday being an adventure, active, going off the beaten track, being indulged int the culture of the people, meeting wonderful like-minded travellers and at this time of the year from July to September an endless summer. Feel free to share the comments of this email to those that should particularly appreciate my big thanks. I will definitely be travelling Intrepid again, a very happy customer! Kind Regards, Leanne Corrie
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Best of Morocco, December 2016
Anne Feeney
Excellent itinerary with a good mix of countryside and cities. We enjoyed drinking tea with local Berbers, and trekking in the Atlas mountains.
Review submitted 22 Oct 2017
Grand Canadian Rockies, July 2017
Anne Feeney
Our Rockies trip was great - beautiful scenery, excellent guide and comfortable accommodation. We had considered self-driving but with this tour we saw so much more, and enjoyed being able to sit back, relax and appreciate the sights.
Review submitted 22 Oct 2017
Indian Getaway, October 2017
Garry Grass
An excellent trip touching on the highlights and sights of Northern India. Sleeper trains and local transport provide a good opportunity to mix with the locals but be prepared for the odd delay, things can run on "India time"...
Review submitted 22 Oct 2017
Inca Trail, October 2017
Rebecca Moore
The Inca Quarry Trail was amazing! Totally recommend it! Difficult hike but made Machu Picchu so much more rewarding.
Review submitted 22 Oct 2017
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More cities in Northeast Florida are reacting to the passage of Amendment 2.
Hundreds of thousands of Floridians can be eligible for medical marijuana next year, with a possible 2,000 dispensaries in business.
But Jacksonville, Neptune and Atlantic Beaches are all considering temporary bans for these businesses, according to our partner Action News Jax.
Jacksonville Beach city manager George Forbes said they're not trying to prevent the dispensaries, but instead will create regulations for where they'll go.
"We're not so interested in having them in the downtown area, and more interested in having them in general commercial zones," said Forbes.
Jacksonville Beach has proposed a one-year ban.
Neptune Beach has proposed a three-year ban.
For medical marijuana dispensaries, our beach cities want to keep the status quo. More at 6 @ActionNewsJax pic.twitter.com/j6Q51mo3fh— Kevin Clark (@KevinANjax) November 30, 2016
Both proposals say the ban provides time for officials to determine how dispensing should be permitted.
They also cite possible negative secondary effects on surrounding land use and communities.
"I think they were just being cautious," said Julie Kelly, who works at BioMax Health Food Store.
She said she doesn't believe beach dispensaries would hurt neighboring businesses, as long as doctors don't over prescribe.
"I don't worry about that at all," said Kelly. "I would think it'd be like any other drug that is regulated by the state and researched."
Council members in Jacksonville Beach will hear the ordinance proposal on Dec. 5.
In Neptune Beach, the ordinance will be heard early next year.
Atlantic Beach records show council members discussed a temporary ban earlier this month, but our calls to the city went unreturned Wednesday.


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Quantico Heading Abroad in Season 3
Alex Parrish, prepare to ciao down: Quantico will shoot part of its Season 3 premiere on location in READ MORE
Alex Parrish, prepare to ciao down: Quantico will shoot part of its Season 3 premiere on location in READ MORE
Prepare for more Harry situations in Quantico's upcoming third season: Russell Tovey will return to the ABC spy drama as a series regular, TVLine has learned. READ MORE
Here's a top-secret piece of Quantico intel ahead of Season 3: Marlee Matlin (Switched at Birth) will be on hand to help Alex & Co. fight the bad guys, TVLine has learned. READ MORE
Quantico is calling a Code Black (producer) on Season 3. READ MORE
Got a scoop request? An anonymous tip you're dying to share? Send any/all of the above to email@example.com
Question: So, what's the deal with Quantico Season 3? Is ABC completely overhauling the show? —Justine
Ausiello: I don't know about a complete overhaul, but READ MORE & GET SPOILED
The winds of change continue to whip through Quantico. READ MORE
Quantico is losing more than just its showrunner.
TVLine has confirmed that original cast member Yasmine Al Massri — who has played twin FBI recruits Nimah and Raina on the ABC drama for two seasons — will not be returning for Season 3. READ MORE
THE PERFORMER | Elisabeth Moss
THE SHOW | The Handmaid's Tale
THE EPISODE | "A Woman's Place" READ MORE
Scorpion closed Season 3 on Monday night with 7.9 million total viewers and a 1.2 demo rating (per finals), ticking up on both counts to mark 14- and 11-week highs. READ MORE
Weeks ago, Quantico creator Joshua Safran told TVLine that the ABC spy drama had shot an ending that he'd cut if word of the show's renewal hit before the finale aired.
As it turned out, though READ MORE & GRADE IT


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Policy, Strategy and Action
Healthy New Towns: Barking Riverside, London and Northstowe, South Cambridgeshire
Barking Riverside and Northstowe are two demonstrator sites approved as part of a commitment in the NHS Five Year Forward View to dramatically improve population health, and integrate health and care services as new places are built and take shape. Catherine represented Care City as co-lead of the Barking Riverside Healthy New Town initiative development phase. This work culminated in a funded delivery plan based on researcher and practitioner input of evidence and good practice alongside extensive community engagement, in partnership with MakeGood, to ascertain local priorities, opportunities and capacities. Catherine continues to provide strategic advice and support to the team, with a particular focus on research. This includes working closely with Professor Nick Tyler of UCL on a suite of projects to optimise access and mobility around the site. In Northstowe, Catherine is working with Chris Blandford Associates and Tim Gill of Rethinking Childhood to devise a play and healthy living strategy which will embed lifelong health, activity and exploration into the new town's physical environment.
In association with Iken Associates.
Built Infrastructure for Older People's Care in Conditions of Climate Change
Durham University's Built Infrastructure for Older People's Care in Conditions of Climate Change (BIOPICCC) was a 3-year research project which worked closely with local authorities to develop strategies to ensure infrastructures and systems supporting health and social care for older people are resilient to the harmful impacts of climate change, particularly extreme or severe weather events. Though the original research focused on older people's care, it has proven relevant to a wider range of services and community resilience more generally. Catherine conducted interviews with participants who were involved in the original research or have subsequently made use of the BIOPICCC toolkit to examine past and present impact and to consider the effects of changing political priorities, public spending cuts and health and social care restructuring. With the Durham team and Climate UK, she then facilitated a peer-to-peer workshop looking at what helps take effective action and what gets in the way.
Funded by Durham University and the EPSRC via the ARCC Network.
Sustainable Development Strategy for the Health and Care System 2014–2020
The Sustainable Development Unit (SDU) is leading the development and delivery of a new strategy to embrace the whole health, public health and social care system and encompass the measures and targets against which progress will be assessed.
Catherine was commissioned to provide specialist advice and support in scoping the social care contribution to the strategy, spanning the consultation process, leadership engagement, strategy development and a sector carbon footprint. She continues to support the SDU in engaging the sector.
Download Sustainable, Resilient, Health People & Places: A Sustainable Development Strategy for the NHS, Public Health and Social Care System 2014–2020.
Read Catherine's guest blog for think tank LGiU on the importance of social care and local authority engagement with the strategy.
Sustainable Social Care Programme
Catherine Max Consulting initiated this major national policy and development programme which was funded by the Department of Health and Social Care Institute for Excellence (SCIE). We identified the need to apply sustainable development principles to social care in response to the imperatives of demography, climate change and economics. We successfully raised awareness of sustainable development and built capacity across the sector through research, conferences, practitioner learning events, and publications.
Our work included a collaboration with Bristol City Council, with whom we explored how personalisation could stimulate the market for environmentally sustainable social care. See our case study report Bristol City Council and Mainstreaming Environmental Sustainability, and Sustainable Social Care and Personalisation: A Guide for Community Engagement, produced in conjunction with uscreates.
For further information about the programme, visit SCIE's sustainability web pages where you can also download our publications.
Read Catherine's guest blog for Age UK: Think Global, Act… Personal: A Sustainable Future for Social Care
Under the Weather: Health and Social Care Adaptation Toolkit
The Environment Agency's Climate Ready service provides tools and information to help businesses and other organisations live with the changing climate, now and in the future. Climate Ready has published Under the Weather, a user-friendly reference resource for the health and wellbeing system to help clinical commissioners, directors of public health and social care, councillors, clinicians, the public and the third sector take action to adapt.
Catherine was the social care expert member of the project's Technical Advisory Group and provided additional advice to consultancy URS who led development of the toolkit.
Under the Weather was launched at events hosted by Climate UK in Manchester and York, in February 2014. Presentations from these events can be found here.
Climate Impacts: Health Risk Assessment for London
We were commissioned by the London Climate Change Partnership (LCCP) to analyse the London-specific risks to public health and to health and social care services of climate change, and to make recommendations for adaptation of service planning and delivery. This was the first ever whole-region risk assessment for the sector. We tested these recommendations at a stakeholder workshop involving commissioners, policy-makers, and estates managers, which has led to a new coalition of cross-sector support for action on health and climate in London.
Read our Risk Assessment and Action Plan.
LCCP's London's Changing Climate—In Sickness and in Health provides an overview of our findings and recommendations for cross-sector action.
Delivered in partnership with Ben Cave Associates and Geofutures.


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Category Archives: Family
Baby Therapy
A new baby is like the beginning of all things: wonder, hope, a dream of possibilities. ~Eda LeShan I know I tend to stray from the supposed theme of my blog pretty often. But today I have a new twist … Continue reading
a walk in the woods
Don't you hate it when you know you really should do something because it's good for you, but you still don't feel motivated to do it? I know I need regular time outdoors in order to feel well, but lately … Continue reading
Posted in Ecotherapy, Family, Walking in the Woods Tagged blahs, bored, inspiration, motivation, photography 4 Comments
Sunset Therapy, Just When I Needed It
I realize I don't write about "nature as therapy"quite as often as I intended. All of my birding, hiking, and kayaking are forms of ecotherapy, but I don't always write about them that way. This weekend, though, I experienced something that … Continue reading
Posted in Ecotherapy, Family, Grief, Travel Tagged ecotherapy, family issues, grief, healing, nature, nature therapy, stress, sun, sunset 1 Comment
So Far, So Good
Well this winter has been extremely mild up until now, so we've been able to get outdoors more often than usual. As a result, my depression hasn't gotten a good hold on me yet, and for that I'm SO thankful. … Continue reading
Posted in Cats, Family, Happiness and Gratitude Tagged adopting a cat, humane society, low VOC paint, non-toxic paint, paint 4 Comments
The Worst Thing Imaginable
I intend to get back to writing about more positive things in my next post, but I hope you'll indulge me one more time as I need to write about something sad again. When I wrote about my brother-in-law's struggle … Continue reading
Posted in Family Tagged brain cancer, cancer, death, love of a family, Ron, so proud of my sister 9 Comments
When Bad Things Happen to Good People
This is difficult to write. Because writing about it means I have to think about it instead of distracting myself as I have been lately. My sister's husband Ron has brain cancer. He's 49 years old, and he's been fighting … Continue reading
Posted in Family, Health Tagged brain cancer, brain tumor, cancer, cancer sucks, caregiving 8 Comments
OLD Family Photos
Last weekend I was thrilled to be able to spend some quality time with my parents, something that happens all too rarely these days. And I think they enjoyed it as much as I did. They dug out some old … Continue reading
Rain, Rain, Go Away!
We've had about 4 cool, rainy days in a row now, and I'm over it. I usually love rain — the sound of it on the roof, the way it cleans and brightens everything, and how it nourishes my flowers. … Continue reading
Posted in Family, Flowers and Gardening, Travel Tagged Chipmunks, Indigo Bunting 1 Comment
A Bird-tastic day at the park
The road commission was working on our road yesterday (what else is new?), and the constant backup beeping of the trucks was driving me absolutely bonkers. The person who came up with that idea for backup beepers should be shot … Continue reading
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LONDON (MarketWatch) -- European stock markets dropped further in afternoon action on Thursday, as European Central Bank President Mario Draghi acknowledged that an expected euro-zone recovery in the second half of the year is "subject to downside risks." Speaking at the central bank's monthly news conference, ECB's monetary policy will remain "accomodative" as long as needed. The Stoxx Europe 600 index SXXP, -0.72% dropped 0.5% to 293.35, after trading around 294.77 before the news conference. The FTSE 100 index UKX, -0.29% lost 0.7% to 6,375.81, while Germany's DAX 30 index DAX, -0.52% fell 0.1% to 7,862.11. France's CAC 40 index PX1, -0.42% slipped 0.1% to 3,752.95.
Read the full story: Europe stocks drop as Draghi addresses economy


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D Pinetrees
The 2-star D Pinetrees Hotel is set just 9.2 km from Dataran Bandaraya, Downtown East and Singapore Turf Club.
All non-smoking rooms including Family Room, Superior Room and Deluxe Room are fitted with free Wi-Fi and climate control.
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I was a little apprehensive about taking Oliver bowling for the first time, but the technology has advanced to the point where a three-year-old can roll a 101. He was given a ramp for launching his ball. Our attendant stuck a hook into our gutters and raised guardrails that would keep all but the wildest shots in play. Bad shots actually do better as they zig-zag back and forth.
Unable to sit through an entire game of Candyland, and usually indifferent to the concepts of winning and losing, Oliver knocked over three pins with his first roll and promptly pressed the 3 button on the scorer's table, all without me explaining the rules.
Unlike the driving games of my youth, in which you'd crash, be thrown from your vehicle, and laboriously shift through your gears again, the driving game in the bowling alley also had guardrails so that it was impossible to drive off the road.
Saturday, May 10, 2008
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Craig Chrest's Executive Recruiting Firm Places Top-Level Execs Despite Poor Jobs Outlook, Report
Employment of top executives is expected to grow 5 percent from 2010 to 2020, slower than the average for all occupations, according to the most recent 2012 Bureau of Labor Statistics (BLS) Occupational Outlook Handbook. Executive HHG, a leading Houston-based executive placement firm headed by former NFL player Craig Chrest is helping top-level executives find permanent job placement—even in a weak economy.
(PRWEB) February 14, 2013
Finding the job you want instead of the first one to come along can be a daunting task in today's economy, and in a sea of corporate mergers and bankruptcies, even battle-tested, top-level executives find the grind and results of a job search to be quite bleak. And, according to the most recent 2012 Bureau of Labor Statistics (BLS) Occupational Outlook Handbook, employment of top executives is expected to grow 5 percent from 2010 to 2020, slower than the average for all occupations.
"These statistics shed light on the reality that executive applicants face even stronger competition for jobs, making it painfully clear that the executive recruiting landscape must change," says Craig Chrest, founder of Executive HHG, a leading Houston-based executive placement firm. The company is helping top-level executives find permanent job placement—even in a weak economy—with a different approach.
The nations' pool of executive-level talent is extensive. For example, a single job posting for an executive position paying just $200,000 yields approximately 750 resumes the first two days and over 2,000 more during the next five days. The reason for such fierce competition for a single job explains Chrest is that "Many CEOs are being displaced on account of corporate mergers, bankruptcies and general downsizing."
Executive HHG is responding to this reality with a different approach. Unlike the usual executive recruitment firms that represent a limited number of employers they have arrangements with, Executive HHG's loyalty is to its client candidates. A specific recruiter works closely with each client to develop a list of target companies and positions, which are then approached through Executive HHG's network of contacts. The company then provides one-on-one mentoring to client candidates for the duration of their job search.
According to CNNMoney.com, only one in 10 people who have been unemployed for the long-term eventually find work. "This is why it is so important to work with a firm that will do more than fax over your resume and make a few phone calls," adds Chrest. He also notes that statistics show that 64 percent of successful executive placements occur through relationships with top decision-makers, not through HR departments. "We have never failed to identify and reach the proper hiring authority on our candidate's behalf."
A longtime Houston resident, Chrest played college football for the University of Wisconsin, was inducted into the UW-Lacrosse Hall of Fame and went on to play professionally for the Green Bay Packers. "Much like football players, job applicants must be able to quickly adapt to changes," he says. "Our firm is helping out-of-work CEOs and executives adapt to the realities of jobs' marketplace and make changes to the game plan that will ultimately help them land the right job."
Judging by published results, Executive HHG's approach seems to be working – in the last year, the company boasted a 74 percent success rate, placing executives into positions paying from $200,000 up to $2.9 million.
For the original version on PRWeb visit: http://www.prweb.com/releases/prweb2013/2/prweb10426590.htmView Comments and Join the Discussion!


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If you read my post about my Mom, you understand that my parents are extremely inspiring and important people to me. I don't know who I would be without either of them…I started this inspiration series with my mom, but now it's time to share a little bit about my 'Faj'…
I realize that nobody is perfect. But when I was growing up, I couldn't help but think that maybe my dad was perfect. There were no outbursts, raised voices, or moments of uncertainty when making a decision (at least none that I was ever aware of). He was poised and controlled. And he always thought carefully before he spoke.
Because my dad has such a unique ability to think every one of his words through before saying them aloud, there was never any turning back. I believed that whatever he said was how things were and how they were meant to be, and I just didn't argue. Except maybe a few times in my teenage years… We'll let those slide ;)
Dad is one of five and while he was a kid, his family moved around quite a bit. Over the years, he formed very solid and close relationships with his siblings. I attribute my closeness to my brothers and sisters to his closeness with his. Every year my dad gets together with his siblings for 'Sibfest'- a tradition that has been passed on to his own kids. Sam, Brit, Lo, and Joe, all flew down to Austin in May and we had our own first 'Sibfest'.
My Dad is also a very modest person. I've never known someone so brilliant to be so subtle about his abilities. He attended Kellogg business school at Northwestern after killing it at Miami of Ohio. He had exceptional grades, a wonderful work ethic, and a dream of supporting a large family.
He has a deep love for fall and nature and the great outdoors… Kind of sounds familiar, right? Yup- I love these things very much too. We would drive up to 'Happy Andy's'- (the family hunting shack) each October for a weekend getaway up north. My mom would stay at home. The 'shack' accommodations were not so suitable for her, so we had a weekend with Dad to ourselves. Some of my favorite childhood memories consist of learning to build campfires, climbing trees, walking through the forest in search of grouse, and telling ghost stories by the fire. The stories were manageable as we all curled up in one big room at night. I had two sisters on each side of me because I always won the middle card placement. Eldest child privileges…am I right?
Another memory of my dad that always crack me up is remembering when he'd come home from work so excited to 'squeeze his babies' that he'd drop his bags to put on 'play clothes' and we'd hear that inevitable snapping, indicating the tickle monster was coming upstairs in search of prey. He had an devilish grin on his face, and a habit of biting his tongue when overjoyed… The minute we'd hear that snapping, we'd all start a convulsion of giggles as we darted into the safety of our rooms. Did I say safety? We were never safe ;) Dad always won and we'd burst into our laughter and screaming fits and I can't say this was a habit my mom really enjoyed… SO LOUD ;) But his excitement to see us always showed how much we meant to him…. The tickle days are over, but the tongue bite on the side of the mouth is always present when everyone is home and he is overwhelmed with happiness…
What I love most about my dad is his deep devotion to his family. Family is the most important thing in the world to him and it shows through his relationships with his siblings, his parents, his wife, and his children. While Eric and I were planning our wedding, we decided to have a display of previous weddings of our family members. You wouldn't believe how excited my dad was to find old photographs of his relatives. Family history is everything to him. And the love of heritage is something I have also adopted from him.
Thank you Dad for being such a fantastic role model for all of us… For letting us figure out our skill sets and dreams… For being at all of our sports games, plays, karate matches, & events… For working so hard and never taking your stress out on us… For your epic roll of the arms dance moves & candid 'duck lips' moments caught on camera… (blame me all you want for that look but I'm pretty sure you've owned it quite nicely)… For always putting family first… For all your love and support over the years… and for being such an authentic, hysterical, wonderful, loving person, through & through.
I love you Dad!
Margie, Marge, Grete, Sharon, Yoda, Maid Merien, Cinderella, & Arielle…
Sorry for that last one Dad… But duck lips HAD to be shared ;)


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Scuba diving in Big Brother
This tiny island is half of the Brother Islands, a popular Red Sea liveaboard dive destination that was named the second-best dive site in the Red Sea and the ninth-best site in the world by CNN in 2012. It is located in about 60km/40mi offshore and is barely visible, but is easily identified by its Victorian stone lighthouse, which towers some 32m/105ft above the island. It is an oblong landmass some 0.4km/0.25mi long, mostly famous for diving with different types of sharks. Here divers can dive down unspoiled walls densely covered by colorful soft corals and huge gorgonians and full of small caves and overhangs. Worth mentioning: the sea conditions can be rough and occasionally cause diving to be canceled. Big Brother also has 2 wrecks, the Numidia and the Aida, lying quite close to each other, which are truly worth exploring.
When to go
It is possible to dive all year round at this site. The best season to dive is from June to August when the sea is usually calm. The water temperature ranges from 23-30C/73-86F.
What to see
In these waters divers will encounter the oceanic whitetip shark, schooling hammerhead sharks, gray reef sharks, silvertip sharks, and even the rare thresher shark. Divers will also swim among other pelagic fish such as barracudas, giant trevallies, tuna, and even magnificent manta rays, as well myriads of colorful reef fish.
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If you are looking to find the best way to mix your favorite protein drink or pre-workout then find the latest Shaker Cups here.
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Posted by: admin | August 14th, 2011
Played: This game was played 23,804 times.
Description: You wanted more levels? You got them! New 20 levels for original Fanged Fun.
Your goal is to help green and red faces get to their corresponding platforms.
A Box can transform into a ball, a ball can transform into a box.
Instructions: Click a box to transform it into a ball, click the ball to transform it back into a box.
Use "R" to restart level.
Tags: Box2d fanged fun Physics puzzle ..
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Air Force Provides Any Service, Anytime, Anywhere, Securely
The Royal Saudi Air Force (RSAF) protects the skies over the Kingdom of Saudi Arabia (KSA). Their challenges are to maintain critical communications links, reduce organizational complexity and cost and deliver new support services. They chose Cisco to overcome these challenges. They have implemented service oriented architecture featuring private self-managed ...Download Now
African Bank Halves Data Center Size
Zanaco is one of Zambia's top banks. It leads the way in areas such as Automated Teller Machines (ATMs) and Internet banking. Their challenges are to create IT platform for growth and simplify admin and upgrade compute. They chose Cisco to overcome these challenges. They have implemented Cisco Unified Computing ...Download Now
IT Solutions Provider Delivers Unified Global Services
Getronics is a Cisco Gold Certified Partner, offering a complete portfolio of integrated IT and communications services for large enterprises and public-sector organizations. Their challenges are to engage with multinational German company to provide superior visibility across installed base, consolidate end-of-life data for more proactive lifecycle management and help ensure ...Download Now
Global Bank Builds Foundation for Highly Secure BYOD
Their challenges are to accelerate Cisco IOS Software standardization in the face of frequent M&A activities, implement coherent security policy to enable more granular controls of approved, suspect, and rogue devices and prohibit noncompliant devices from accessing critical. They chose Cisco to overcome these challenges. They have implemented gain Cisco ...Download Now
Data Center Provider Boosts Hosting Capability
OEtker Daten und InformationsVerarbeitung (OEDIV) is a data center application hosting business belonging to Dr. Oetker, the German multinational conglomerate. Their challenges are to reduce costs while maintaining quality of service, attract new hosting customers and improve time to market. They chose Cisco to overcome these challenges. They have implemented ...Download Now
Print and Marketing Services Provider Simplifies Collaboration and Customer Care
A global company, Vistaprint provides high-impact, personalized products and electronic services for micro businesses and the home. Their challenges are to keep workforce connected as company expands globally, connect customers globally to first available agent with the right skills and make sure customers can reach employees and employees can reach ...Download Now
Growing University in Namibia Moves to Next-Generation Security
At The Polytechnic of Namibia has a 13,000-student university with 11 offices across the country. Their challenges are to prepare network for anticipated doubling of student body size, strengthen network security against increasing infections and attacks and simplify security implementations and management for limited staff. They chose Cisco to overcome ...Download Now
Making Business Expansion Count
iland is an award-winning enterprise cloud infrastructure provider with eight datacenters located in U.S. and Singapore. Their challenges are to enable rapid scalability and flexibility to address complex customer use cases, maximize productivity through automated, repeatable data center deployment processes and cost-efficiently expand European cloud operations to address needs of ...Download Now
Protecting Against Security Threats, Streamlining Service Delivery
The Gobierno de Castilla-La Mancha, the Regional Government of Castilla-La Mancha in Spain, provides health, education and administration services for a widely dispersed population of more than two million residents. Their challenges are to streamline delivery of regional government's public services and update, simplify email management with easy-to-deploy email security ...Download Now
Creating a Global Security Model
MONDI Group International keeps the paper and packaging industry moving. Their challenges are to promote benefits of flexible working without compromising IT security and address growth in devices and guests seeking network access. They chose Cisco to overcome these challenges. They have implemented Cisco TrustSec with Cisco identity services engine. ...Download Now


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Tuesday, 15 December 2009
Drog sees RED
1 December was World AIDS Day – Niketown on Oxford Street has "gone RED", as have their flagship shops around the world. They've produced red laces which all Nike football players are wearing. Their shops have red windows. The sales of these laces will raise money for the Global Fund to fight AIDS, raise awareness about RED and AIDS and help secure more public funding for the Global Fund in the US. RED's already raised over $140m.
Didier Drogba came to the launch, alongside Bono whose idea RED was. The Ivorian man mountain likes his RED laces - in the photo above he's scoring the first of 2 goals for Chelsea against Arsenal while wearing them.
"Drog sees RED" made it on to Page 3 of The Sun, directly below Poppy, 19 from Swindon. Unfortunately Poppy didn't have anything to say about World AIDS Day. She did have very small pants though. Her comment box featured her opinion on the front page story about a family of Somali asylum-seekers who have been given a big house in Westminster.
Biking through a cold but clear London I passed the fountains in Trafalgar Square spraying red water into the night sky while the giant London Eye shone a bright red arc over Whitehall. I've lost my gloves and wear socks on my hands instead. To regain sensation in my fingers I got a RED coffee from Starbucks. They've learnt from last year's novelty, ginger flavoured coffee that RED coffee is best served in a red cup rather than the coffee literally being red.
The MP I went to meet turned out to be an Arsenal supporter. He wasn't as enthusiastic about Drogba's red laces. He did agree that the World Cup in South Africa makes 2010 a year when the world will see Africa differently. He said the right things about politicians keeping their promises to the world's poor despite the economic crisis.
Will Drogba and the rest rise to the test? South Korea got to the semi-final when they hosted the World Cup and they were rubbish. The mighty elephants of Ivory Coast, lions of Cameroon and Bafana Bafana of South Africa should show Africa at its best up against the superpowers of Brazil, tricky Italians and cheating French: a continent fighting massive odds with an uncertain present and exciting future.
Cycling home beneath a full moon I looked north to the alien beacon that is the BT Tower. It was bright RED.
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Mitel Surpasses Three Million Cloud Subscribers
Mitel® (Nasdaq:MITL) (TSX:MNW), a global leader in enterprise communications, announced today the addition of more than one million new cloud subscribers in 2016, tipping its cloud business past the three million user mark to reach another industry milestone. The company still holds the lead in business cloud communications with more than twice the number of subscribers as its nearest competitor.With increased global coverage, Mitel continues to bolster its cloud offerings, giving even more businesses and multinational companies access to the cloud communications provider one in four cloud users trusts most. A recent Gartner report also scored Mitel highest in satisfying hybrid unified communications use case requirements.For a limited-time, Mitel is offering a special promotion for Avaya users or anyone actively considering investing in an Avaya solution in 2017. Purchase a new MiCloud solution and get three months of Mitel cloud service free along with professional installation.Q
uotes"Moving our communications to the cloud gives us an affordable and highly reliable solution that allows us to focus on our business without worrying about downtime or dedicating resources to maintenance," said Casey Gubler, Controller, Lad Irrigation. "Mitel's cloud platform also gives us advanced features that are easy to use and accessible when we're mobile, so we can enjoy the same in-office experience, even on the road.""Businesses around the world are turning to cloud communications to seamlessly connect their workforces, enhance customer service and simplify IT management," said Jon Brinton, EVP and President, Mitel Cloud Division. "Mitel delivers the stability and expertise to provide them a better path forward to hybrid and pure cloud solutions at a pace that's right for them and with the assurance their investment is futureproof."
Important Facts
Mitel offers cloud services in 40 countries supported by 14 top-tier data centers strategically located around the world.Mitel is the only brand to appear in all five Gartner Magic Quadrants for business communications.Mitel is an exhibitor at Enterprise Connect March 27-30 in Kissimmee, Fla.; booth #518.
Related Materials
Download free copies of the "Cloud Communications for Dummies" and "Team Collaboration & Communications for Dummies" eBooks.Social Media
Twitter: Mitel surpasses three million #cloud subscribersTags/Keywords
Cloud Communications, Collaboration, Unified Communications*Gartner's Critical Capabilities for Unified Communications as a Service (UCaaS), Global Published: 28 November 2016.
Gartner does not endorse any vendor, product or service depicted in its research publications, and does not advise technology users to select only those vendors with the highest ratings or other designation. Gartner research publications consist of the opinions of Gartner's research organization and should not be construed as statements of fact. Gartner disclaims all warranties, expressed or implied, with respect to this research, including any warranties of merchantability or fitness for a particular purpose.
About Mitel
A global market leader in enterprise and mobile communications powering more than two billion business connections, Mitel (Nasdaq:MITL) (TSX:MNW) helps businesses and service providers connect, collaborate and provide innovative services to their customers. Our innovation and communications experts serve more than 60 million business users in more than 100 countries. For more information, go to www.mitel.com and follow us on Twitter @Mitel.Mitel is the registered trademark of Mitel Networks Corporation.All other trademarks are the property of their respective owners. MITL-CContact Information
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Lauren Moores » VP Analytics, Dstillery
Lauren is a data guru with over 20 years of experience in data strategy, science, and creation in different information and technology industries. At Dstillery she runs all things analytics and is an active industry speaker and writer, particularly on mobile analytics.
Most recently, Lauren was named the silver award winner of the ARF Great Mind Award, and was invited by I-COM Global Forum for Marketing Data and Measurement to sit on its Data Science Board. Additionally, Lauren is involved with a myriad of top Technovation 2014, NYTechWomen, CTIA Innovation Council, Similar Group, Unbound Concepts, and Jumpshell.
She began her career at DRI/McGraw Hill as an economist before earning her PhD in Economics at Brown University. Drawn to the internet's power to provide information and services, she left research and teaching to take on a role managing the science, data assets and data product teams at Compete,where she also built large, multi-sourced global digital consumer panels. Most recently, Lauren led the vision and development of data science at EveryScreen Media, a start-up mobile RTB and audience technology company acquired by Dstillery.


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Abu Dhabi-based Brazilian designer and artist Fábio Araujo has a fascination with abandoned places – the mystery of where the man made clashes with the natural to create unique colors, textures and compositions.
These places are the subject of his series, aptly titled "Abandoned Places," in which he uses a series of digital manipulations to create small islands floating within and contrasting with their clean, solid backgrounds.
Other works by Araujo include "Favela," where the Brazilian housing typology has been reimagined as located within the sky, and miniature models of scenes and buildings including the Burj al Arab hotel in Dubai.