text:
- Research
- Open Access
Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue
© Broderick et al.; licensee BioMed Central Ltd. 2012
- Received: 4 May 2012
- Accepted: 7 September 2012
- Published: 13 September 2012
As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively.
Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection.
Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls.
These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.
- Cytokines
- Infectious mononucleosis
- Chronic fatigue
- Classification model
Chronic Fatigue Syndrome (CFS) is a complex and poorly understood illness that affects between 1 and 4 million individuals [1, 2] and costs an estimated $35 billion per year in lost productivity and health care [3, 4]. Persistent and unexplained fatigue has been observed as a sequela of acute infection since the first half of the 20th century and the period's notable outbreaks of infectious disease (e.g., polio epidemics, influenza pandemics). From 1934 to 1984, there were several reports of infectious disease outbreaks simulating poliomyelitis [5, 6] though no causal pathogen was isolated from the majority of the cases. Clinical investigation of individuals who did not recover several years after initial infection showed persistent symptoms of fatigue, sleep disturbance and cognitive impairment [7, 8]. Following an outbreak investigation in 1984 by the Centers for Disease Control and Prevention (CDC) in Incline Village, Nevada [9], an international group of medical experts defined this protracted post-infection illness as chronic fatigue syndrome (CFS) [10]. Since then, post-infection illness that lasts for more than six months is a central component of CFS, and studies have shown that the incidence of CFS following infection with a number of different pathogens is about 10% [11–14]. The pathogens that most commonly lead to CFS in prospective studies are those that cause infectious mononucleosis (IM)/glandular fever (mainly Epstein-Barr virus (EBV); occasionally cytomegalovirus (CMV), human herpesvirus 6, hepatitis A, and adenovirus [11], Q fever and Ross River virus (mainly in Australia [13]), enteroviruses [15] and parvovirus B19 [16, 17]. Indeed in recent work by Kerr and colleagues, antibody testing for EBV, enterovirus, Coxiella burnetii (causative agent of Q fever) and parvovirus B19 revealed evidence of subtype-specific relationships for EBV and enterovirus, two of the most common infectious triggers of CFS/ME [18].
There remains therefore an overwhelming body of evidence reinforcing the link to an infectious etiology in at least a subset of CFS patients, despite the fact that specific viral serology are not required for diagnosing CFS [19, 20]. Specifically, there is a notable and long-standing association of CFS with EBV infection. In our previously published analyses of the adolescent cohort presented here [14, 21–24], we reported a diagnosis of CFS at 6, 12 and 24 months following IM, in 13%, 7% and 4%, of the subjects respectively. Ninety percent of CFS subjects at 6 months were female as were all cases at 12 (n = 22) and 24 (n = 13) months following IM. This is consistent with the rates observed by Buchwald and colleagues (2000) [12] who found 12% of subjects had not recovered and were reporting symptoms of fatigue and impaired functioning 6 months following onset of IM, 76% of whom were female. Nearly identical results were also reported in an Australian cohort where 11% and 9% of subjects satisfied the case definition for CFS at 6 and 12 months following onset of IM, Q fever and Ross River fever (RRF) [13].
Investigators have sought to understand the underlying causes of these persistent symptoms by surveying immune signaling in the CFS patient population. Early measurements of cytokine concentrations in blood samples from this broader population produced widely discordant results due mainly to differences in case definition and laboratory protocols [25]. Limiting factors also include the focus on a varied and narrow selection of cytokines [26] as well as a conventional univariate analysis that does not account for the context-specific expression of cytokines [27]. Only one previous study has prospectively evaluated cytokine production in CFS patient populations where a uniform infectious trigger was supported by serology. Hickie et al. (2006) [13] measured the concentrations of 8 cytokines: IL-1b, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ in serum and culture supernatants of peripheral blood mononuclear cells collected 1, 2, 3, 6 and 12 months following the acute illness (IM, RRF or Q fever). The participants were 22 subjects with confirmed PI-CFS (11 EBV, 6 RRV, and 5 Q fever) and 42 control subjects (17 EBV, 14 RRV, and 11 Q fever) matched for age from the same cohort who had recovered within 6 weeks of symptom onset. The analyses were performed on all PI-CFS subjects as a single group, combining the 11 EBV patients with those infected by a virus uncommon outside Australia. They found no significant differences between PI-CFS cases and recovered controls in serum or culture supernatants [28]. However, serum cytokine levels were almost exclusively below the assay detection limit (8–15 pg/ml) and supernatants were cultured from cryopreserved PBMCs. As a result several unanswered questions remain. For example, do key CFS-specific cytokines remain unmeasured? Perhaps most importantly, could PI-CFS cytokine signatures reflect pathogen-specific (and gender-specific) variations in immune response? If so these may be lost when pooling subjects with different infectious triggers (and different genders).
In an attempt to address some of these questions, this secondary analysis has focused specifically on a group of female adolescents diagnosed PI-CFS as the result of a uniform and known pathogen, namely EBV. An extended survey of 16 cytokines was conducted in plasma using a modified chemiluminescent assay [27] and identified significant differences in IL-8 and IL-23 concentrations in the patient group at 24 months post-infection. Because cytokines are expressed in a coordinated fashion we also extended the analysis beyond the traditional univariate analysis to investigate combinatorial effects across multiple cytokines. Taken together, a classification of subjects based on levels of IL-2, 6, 8 and 23 supported assignment into the patient or control group with an accuracy exceeding 80% when applied relative to interferon gamma (IFN-γ) concentration. Interestingly the latter did not differ significantly in expression level across subject groups.
Cohort and clinical assessment
The cohort consisted of 301 adolescents recruited from the greater Chicago area upon diagnosis of monospot-positive acute IM, the presumption being that the vast majority of these cases were caused by EBV infection. Details of this cohort may be found in a recent report by Katz et al. (2009) [14]. In brief, adolescents were identified via school nurses (middle school, high school and college/university), pediatric practices, including the Pediatric Practice Research Group and the Virology Laboratory of Children's Memorial Hospital. All prescribed treatments were recorded. Six months following their IM diagnosis, 286 (95%) subjects completed a telephone-based screening interview using the CFS Screening Questionnaire [29]. Based on the screening interview, 70 of these adolescents (24%) were assessed as not fully recovered. A clinical evaluation was completed on 53 (76%) of these 70 not fully recovered adolescents; 12 refused, 3 had exclusionary diagnoses and 2 did not meet study criteria. There was no significant difference in sex, family socioeconomic status or subject age between the group that completed the 6-month evaluation (n = 53), the group (n = 12) that refused and the group (n = 5) that was excluded (data not shown). Following the 6-month clinical evaluation, 39 of the 53 not fully recovered subjects who underwent clinical evaluation were classified as having CFS (13% of the original sample of 301 adolescents). Compared with the other 262 enrolled subjects in the cohort, 35 of the 39 subjects with CFS at 6 months were female (90%, vs 68%, p = 0.01 by Fisher's exact test). There was no difference in race or socioeconomic status between the entire cohort and the subjects who went on to develop CFS (data not shown). Among the 14 other subjects completing the 6-month clinical evaluation, 1 had recovered between the time of the phone interview and the time he/she was seen in clinic and 13 were classified as CFS explained. There was no difference in family socioeconomic status or subject age between the group diagnosed with CFS (n = 39) and the group (n = 13) with CFS-explained (data not shown).
Thirty-six subjects diagnosed with CFS at the 6-month evaluation were re-evaluated at 12 months (3 were lost to follow-up): 11 recovered, 3 were now classified as CFS-explained, leaving 22 with a diagnosis of CFS (7% of the original sample; all females). At the 24-month evaluation, 3 more subjects with CFS were lost to follow-up since the 12-month evaluation. Of the 19 remaining subjects diagnosed with CFS at 12 months: 6 more recovered, 2 developed a reason for their CFS, 1 subject thought to have recovered at 12 months developed symptoms again and was reclassified as CFS, and 1 subject thought to have CFS-explained at 12 months now met criteria for CFS and had no predisposing reason, leaving 13 subjects (all females) who were classified as CFS 24 months following monospot-positive IM (4% of the original sample of 301 adolescents). Following the IM diagnosis, a telephone-screening interview also identified 50 recovered controls willing to come for a clinical evaluation. Adolescents who had not fully recovered and recovered controls underwent evaluation 6, 12 and 24 months post-IM. There was no difference in age, race or socioeconomic status between recovered adolescents who were and were not used as controls subjects (data not shown). At the 6-month evaluation recovered and non-recovered subjects were evaluated by 1 of 2 physicians experienced in diagnosing CFS (BZK or an adolescent specialist). At the 12 and 24-month visits, the subjects were evaluated in their home with the same blood and urine testing and the same history, interviews, and self-report measures used at six months, by a trained interviewer. All aspects of the study were approved by the Institutional Review Boards of Children's Memorial Research Center and the College of Applied Sciences of the University of Illinois at Chicago. Secondary analysis of the biological samples and data was reviewed and approved by the Institutional Review Board of the University of Alberta. Diagnosis of CFS was based on the revision by Jason et al. (2006) [30] of the international CFS case definition [20], itself a revision of the of the Fukuda criteria [19], although all patients also met the international case definition of CFS [20]. When a well-recognized underlying condition such as primary depression could explain a subject's symptoms then that subject was classified as having "CFS-explained", and these subjects were not included in the analysis. Primary depression was defined based on the Structured Clinical Interview for the DSM-IV Child Version.
The clinical evaluation included laboratory tests to rule out medical causes of CFS (e.g., chemistry panel, complete blood count, erythrocyte sedimentation rate, liver chemistries, urine toxicology, urinalysis and thyroid function tests). The examining physician at 6 months made a diagnosis of CFS, CFS-explained, or recovered on each subject. These diagnoses were then blindly reviewed by an expert panel using the Jason revision for pediatrics [30] of the Fukuda criteria [19] before being permanently assigned to a subject. Each subject also completed the Chalder Fatigue Scale at 6, 12 and 24 months [31], along with the Youth Medical Questionnaire, Modifiable Activity Questionnaire, Sleep Assessment Questionnaire, and the Structured Clinical Interview for the DSM-IV Child Version, Child/Young Adult Behavior Checklist, Child/Young Adult Self-Report, and Life Events and Difficulty Questionnaire [30]. At 24-months post-IM onset, 13 subjects satisfied the criteria for CFS, all of whom were young women. Plasma samples were available for n = 9 of these 13 CFS patients 24-months after diagnosis with IM and 12 recovered controls, matched as closely as possible to the subjects with CFS by gender, age (+/- 1 year) and Tanner stage (4 or 5).
Laboratory measurements
Morning fasting blood samples were collected into ethylene diamine tetra acetic acid (EDTA) anticoagulant tubes. Plasma was separated within 2 hours of collection and stored at -80oC until assayed. We measured 16 cytokines in plasma using Quansys reagents and instrument (Quansys Biosciences, Logan, Utah) in the same way as reported previously in a larger cohort of CFS subjects with unknown etiology and illness trigger [26]. The Quansys Imager, driven by an 8.4 megapixel Canon 20D digital SLR camera, supports 96 well plate based chemiluminescent imaging. The Q-Plex™ Human Cytokine - Screen (16-plex) is a quantitative enzyme-linked immunoabsorbent assay (ELISA)-based test where sixteen distinct capture antibodies have been absorbed to each well of a 96-well plate in a defined array. The range of the cytokine concentrations used in the standard calibration samples were adjusted for each cytokine along with sample exposure time to provide the most reliable comparison possible between CFS patients and controls across the range of cytokine concentrations known and expected in plasma. For the standard curves, we used the second order (k = 2) polynomial regression model (parabolic curve): Yp = b0 + b1X1 + b2X2.. + bkXk, where Yp is the predicted outcome value for the polynomial model with regression coefficients b1 to bk for each degree and y intercept b0. The standard sample concentrations used to establish the calibration curves for each cytokine are listed in Additional file 1: Table S1; these confirm that the concentrations reported in study subjects are within the calibrated range for this assay.
Statistical analyses
Comparative statistics
Each plasma sample was run in duplicate. To compare subject-to-subject variation with replicate error both the parametric n-way ANOVA and the nonparametric Kruskall-Wallis tests were used. Results presented in Additional file 1: Table S2 indicate that variations separating individuals was statistically greater than replicate error for most cytokines in at least one subject group or the other. The parametric n-way ANOVA applied to log-transformed values was generally more sensitive to these differences than the Kruskall-Wallis test. Replicate error in the measurement of IL-1a, IL-10 and IL-17 did not support subject-to-subject resolution within either group regardless of the statistical test used. These were nonetheless adequate for use in comparisons across patient groups as a whole.
To assess the significance of differences in the mean expression of individual cytokines separating subject groups we used a standard parametric t test after performing a logarithmic transformation. In conjunction with this a nonparametric Wilcoxon rank-sum test was used to compare the difference in group-wise median expression for each cytokine. Values below detection limit were replaced with the lowest concentration recorded for each specific cytokine within each subject group.
Classification analysis
As an extension of this group-wide analysis of expression levels, cytokines were ranked according to their classification of individual subjects based on their associated receiver operating characteristic (ROC) curves and on the U-statistic of a two-sample unpaired Wilcoxon ranksum test. In addition to an unadjusted ranking, a relative ranking was also computed that accounted for the cross-correlation (CC) existing between individual cytokines. In this adjustment correlation information was used to reweight the Z value of a candidate cytokine using Zi (1-α ‾r ij), where ‾rij is the average of the absolute values of the cross-correlation coefficient between the candidate i and all previously selected cytokines j = 1 through i. The weighting factor α (alpha) is a scalar value between 0 and 1. According to this adjustment a large value of ‾rij outweighs the significance statistic Z making new candidates that are highly correlated with previously ranked cytokines less likely to be selected next.
The use of cytokines in combination with one another was also considered. For this, linear discriminant classification models were constructed iteratively using randomly selected subsets of cytokines and their performance evaluated. All cytokines were normalized to have a mean value of 0 and a variance of 1.0. Classifiers were evaluated based on their overall error rate (incorrectly classified samples / total classified samples) in assigning subjects to their proper diagnostic group. Only classifiers with overall error rate of less than 20% were accepted into the pool of candidates. In addition the posterior probability of the discriminant analysis was used to invalidate candidate class assignments with low confidence (< 0.90) and label any such instance as an inconclusive classification. Furthermore a strict linear classification model was selected to favor subsets of cytokines that were minimally redundant. Traditional ordinary least squares models will perform poorly when correlated or collinear terms are used together due to variance inflation [32]. Final correction of the linear classifier for collinearity in the selected cytokine subsets was performed using a diagonal covariance matrix estimate. According to this model an observed row x from the sample array is classified into group I rather than group J if 0 < B0 + x*B, where the coefficient vector B and intercept vector B0 are estimated from the data.
In order to assess the robustness of models constructed using the all-possible-subsets approach described above, an analysis of this data using a sequential stepwise variable selection [33] was also conducted. Using this algorithm, a linear classification model was constructed by selecting cytokines sequentially based on their respective partial-F test values. Cytokines with a p(partial F) < 0.05 were selected for recruitment into the regression model while those currently in the model but showing a p(partial F) > 0.10 were pruned. All calculations described above were performed using the classify, classperf, rankfeatures, randfeatures and stepwisefit functions available in the MatLab Statistics Toolbox and the MatLab Bioinformatics Toolbox (The MathWorks, Inc., Natick, MA).
Cytokine expression in PI-CFS patients
Ranking individual cytokine markers
Individual Cytokines as Illness Markers
Ranked Features PI-CFS vs Ctrl**
CC weight alpha=0
U statistic
Ranked Features PI-CFS vs Ctrl**
CC weight alpha=1.0
U statistic
A candidate cytokine-based signature for IM-induced chronic fatigue
Performance Characteristics 1 of Subject Classification using Cytokine Combinations
Optimal Linear model subset
Top ranking AUC with CC correction
Top ranking U statistic with CC correction
Classification based on IL-2, 6, 8, 23, IFNg
Classification based on IL-2, 5, 8, 13, 23
Classification based on IL-5, 23, 8, IFNg, TNFb
Linear cw 90% Conf
Linear uncorrected
Linear cw 90% Conf
Linear uncorrected
Linear cw 90% Conf
Linear uncorrected
Correct Rate
Error Rate
Inconclusive Rate
Classified Rate
Positive Predictive Value
Negative Predictive Value
Positive Likelihood
Negative Likelihood
Even though IL-5 ranked highly in terms of individual performance it was not selected as a contributor to the classification model. To explore this further we examined the correlation of IL-5 with other cytokines. The cross-correlation patterns existing between cytokines in the PI-CFS patient set as well as in the recovered control group are presented in Additional file 1: Table S4. These indicate strong and significant (p < 0.05) correlations between IL-5 and IL-23 as well as with IFN-γ in the PI-CFS patient set (r = 0.65, 0.77; p < 0.01). Truncation of these terms and substitution with IL-5 into the random subset model was explored as a strategy for alleviating these redundancies. In all cases classification performance was significantly reduced (Additional file 1: Table S5). This suggests that IL-23 and IFN-γ are better suited than IL-5 to support class assignment based on IL-2, 8 and 6.
Stepwise and Consensus Classification Models
Classification based on
Stepwise model of IL-1a, 6, 8,13, 23
Consensus model of IL-6, 8, and 23
Minimal model of IL-6 and 8
Correct Rate
Error Rate
Inconclusive Rate
Classified Rate
Positive Predictive Value
Negative Predictive Value
Positive Likelihood
Negative Likelihood
In this work we studied a population of adolescents that developed CFS as a sequela of monospot-positive IM and compared them to control subjects who recovered normally from the same infection. Approximately 4% of subjects (or 13 individuals) diagnosed with IM fit the case definition for CFS at 24 months, a number consistent with other prospective studies of infectious onset CFS [12, 13]. In comparing the concentrations of 16 cytokines between cases and recovered controls we found significantly different levels of IL-8, IL-23 and possibly IL-2 and IL-5 in plasma samples from CFS patients. Increased IL-8 and decreased IL-5 is a pattern also seen asthma [34] and in B cell chronic lymphocytic leukemia (B-CLL) [35]. Most striking were differences in IL-23, a cytokine expressed by dendritic cells and macrophages. Though not required for the generation of Th17 cells from naïve CD4+ T cells, IL-23 is nonetheless essential for the full and sustained differentiation of the Th17 cell subset [36]. Median concentration of this cytokine was significantly lower in patients with CFS than in recovered controls. IL-23 expression is highly inducible in PHA-stimulated CD4+ cells, in particular when primed with IFN-γ, suggesting a potential role for IL-23 in Th1 response [37]. We found decreased expression of IL-23 in CFS patients despite comparable levels of IFN-γ. In addition we found levels of IL-17 to be similar despite elevated levels of known antagonist IL-2 [38]. Consistent with this, our previous analysis of cytokine expression in a population of adult subjects with CFS of unknown etiology [27] indicated an abnormally subdued IL-23/Th17/IL-17 response to elevated levels of known inducers IL-1b and IL-6 [39].
The above-mentioned discrepancies emphasize the importance of immune context. Indeed it was necessary to use the combined expression of 5 cytokines to support a robust separation of patients from recovered controls. Ultimately the context linking the expression of these cytokines arises from one or several basic immune processes acting in concert. Here the choice of cytokines in both the all-possible-subsets and stepwise regression models is interesting in that the majority of these are either directly or indirectly related to Th17 response [39]. In this analysis IL-6, 8 and 23 were selected by two different statistical approaches, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. It is interesting to note that neither IL-1a, nor IL-6 or IFN-γ were differentially expressed across groups even though they contributed significantly to the classification of these subjects. IL-1, 6 and 23 are known inducers of Th17 response, which in turn is a producer of IFN-γ [39]. Conversely IL-2 is generally known as a Th17 antagonist [38]. Liu et al. (2007) [40] describe a mechanism by which IL-1 induces the production of IL-23 via NF-kappa B activation, which in turn promotes the production of IL-6 and 8 in human fibroblast-like synoviocytes from rheumatoid arthritis patients. Though this is still poorly understood, recent evidence in animal models supports a role for EBV and EBV-inducible genes in the pathogenic modulation of Th17 response [41, 42]. This may involve TLR9 which has been shown recently to play a significant role in the recognition of EBV by primary dendritic cells (DC), as indicated by a marked inhibitory effect on their synthesis of IFN-α, IL-6, and IL-8 [43]. Collectively the current analysis, as well as results from our previous work [27], suggests that illness-specific differences in the regulation of Th17 response may be a shared component in a significant subset of CFS cases.
When comparing this work with results from other studies it is important to remember the type of sample and the specific patient population studied. For example, recent work by Brenu et al. (2011) [44] demonstrated higher levels of IL-10, IFN-γ and TNF-α in CFS. However this was measured in mitogen-stimulated CD4+ cell cultures not in plasma. Similar in vitro protocols were used in earlier work by Amel Kashipaz et al. (2003) [45] and Skowera et al. (2004) [46]. Using the same sample type and laboratory protocol applied here, we recently reported higher levels of IL-5 and lower levels of IL-8 in CFS subjects compared to healthy controls, while levels of IL-23 showed little difference [27]. However both the work of Broderick et al. (2010) [27] and Brenu et al. (2011) [44] were conducted in a much broader CFS patient population where the illness trigger was not uniform. In addition the control population consisted of otherwise healthy individuals not individuals recovering from acute infection. Estimates of the number of patients with CFS who can date their illness to a specific (presumably infectious) acute illness range from 20- 90%, with the highest percentages being recorded in adolescent populations [8, 47–53]. Accordingly our current results align closely with those of another study conducted specifically in a post-infectious patient population by Vollmer-Conna et al. (2007) [28]. The authors found no differences in the concentrations of IL-1b, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ analyzed in serum. With the possible exception of elevated IL-2, we also did not find differences in the levels of these cytokines. Levels of IL-5, 8 and 23 were not measured in this earlier study.
Limitations of our current study include the fact that it reports on a small cohort. This is important when considering the general applicability of our statistical classification model in particular. The hope is that this subset of subjects is somewhat representative of a larger PI-CFS patient population. CFS is well known for its heterogeneous presentation; however it can be argued that much of this is the result of varied etiology and unknown triggers. Our results are derived from a prospective study and constitute an important first look at the molecular phenotyping of persistent fatigue in a cohort with a uniform and known infectious trigger; namely infectious mononucleosis. While this trigger does not explain all presentations of CFS, it does represent a significant subset of patients, in particular in the pediatric population. Moreover though specific to the EBV pathogen, elements presented here may also be of relevance to other forms of CFS with an infectious etiology. Constraints such as these further emphasize the importance of prospective studies and the need for much larger initiatives of this type in this and related patient populations.
In conclusion, the co-expression profile of 5 of 16 cytokines measured in the plasma of subjects recruited in a 2-year prospective study of mononucleosis-induced chronic fatigue syndrome readily discriminates cases from recovered control subjects and describes an atypical immune response in these individuals. In particular, irregular patterns of co-expression in IL-6, 8 and 23 were identified using two distinct statistical methodologies. These differences were especially evident when cast in the context of IL-1a, IL-2 and IFN-γ. This evidence points to a possible dysregulation of the innate system's priming of the appropriate adaptive Th17 response in these subjects.
This analysis was funded by the CFIDS Association of America grants to G Broderick, BZ Katz and NG Klimas; cohort recruitment and assessment was supported by grants from the US National Institute of Health, including R01 HD043301-05 (PI R Taylor), R21AA016635 (PI M.A. Fletcher) and R01AI065723 (PI MA Fletcher); and R01AI065723 (PI MA Fletcher); the US Department of Veterans Affairs, Merit Award to NG Klimas.
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- Brenu EW, van Driel ML, Staines DR, Ashton KJ, Ramos SB, Keane J, Klimas NG, Marshall-Gradisnik SM: Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Transl Med. 2011, 9: 81-10.1186/1479-5876-9-81.View ArticlePubMedPubMed CentralGoogle Scholar
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Cops: Deliveryman sells gas from his truck
The owner of a gas delivery company sold fuel directly from his tanker to drivers in Ronkonkoma Sunday night, Suffolk police said Monday.
Robert Faulkner, owner of Farmingville-based Direct Marine Fuel Corp., charged $4.80 a gallon from his tanker at the Lake Shore Plaza on Portion Road, police said. Sunday night, more than 100 vehicles were gathered in the shopping center and along Portion Road to buy Faulkner's gas when Sixth Precinct officers arrived, police said.
Faulkner, who primarily delivers fuel to vessels and to Verizon, said he had originally arranged to fill up friends' cars at the plaza, but saw an opportunity in the long lines at the gas station across the street. He even paid five friends to keep order in the lines, he said.
He denied he was breaking any law, saying his business permits allow him to distribute fuel and that town officials should "bend the rules" in the crisis.
"I had an opportunity to make more money," Faulkner said. "I'm not hiding that fact, but you know what? I was helping people in the process."
He said he had waited three hours Sunday at a petroleum wholesaler's Holtsville location to fill his tanker with about 2,800 gallons of regular fuel.
An estimated 800 to 900 gallons was sold before police arrived, Faulkner said. One of the customers, he recalled, included an elderly woman who said she had waited futilely in three different lines in three days.
Faulkner, 48, of 10 Antrim Lane, Farmingville, was issued town summonses for handling flammable liquids without a permit and also for improper dispensing of flammable liquids, police said. The summonses were from a Brookhaven Town fire marshal and town building and fire prevention official, police said.
The New York State Department of Taxation and Finance was notified, police said.
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Official Music Video: Travis Barker – "Jump Down" (featuring The Cool Kids)October 13th, 2010 by @E_Wish1 | Alternative/Indie, Hip-Hop/Rap, Music Video |
The music video above is of Travis Barker's "Jump Down" featuring The Cool Kids off Barker's upcoming album, Give The Drummer Some. I love this video because not only does Travis tear it up, but it is entirely filmed at the Venice Beach Boardwalk which was a great place to kick it with the homies growing up. What do you think of the music video?
Credit TMG for me coming across this video.


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NFL Week 1: What We Learned In The AFC [OPINION]
Now that Week 1 of the 2012 NFL season is in the books, what exactly did we learn, if anything?
AFC East:
NY Jets- After what has to be considered one of the worst pre-seasons, the Jets showed us why the pre-season doesn't matter. Even if it was Buffalo, Mark Sanchez and every part of the Jets looked to be in mid season form. Now lets see what happens on Sunday in Pittsburgh.
New England- Tom Brady was Tom Brady, and the rest is exactly what everyone has come to expect from the Patriots and the Hoody. But, there is a bonus this year and that would be Steven Ridley. Could he be the answer to what the Pats need to put them over? We will have to wait and see.
Buffalo- With Fred Jackson on the shelf for at least 3 weeks and David Nelson gone for the year with a torn ACL, all the defensive moves need to really pay off now. For some reason, I don't see C.J Spiller doing what he did on Sunday every week.
Miami: Did you see HardKnocks?
AFC North:
Baltimore: What a performance in the second half on Monday. If Flaco continues to back up his "I am an elite quarterback" statement and the defense plays the way it played, this team could be a real threat come January.
Cincinnati: Lets hope we see the team that showed up in the first half more than the team that played the second half. The last thing this franchise needs is a nose dive after last season.
Cleveland: The Browns made their bed when they chose to go with Brandon Weeden. There is no turning back now. If Weeden can find his receivers, Trent Richardson is going to see 8 in the box for the rest of the year and he may not make it through it. Plus, losing Hayden for 4 games doesn't help.
Pittsburgh: The Steelers are still in the top of the AFC and had they not run into a buzz saw named Peyton Manning, they just might have gotten the win and Denver.
AFC South:
Houston: After a slow start, the Texans made Miami look silly. This year the Texans are going to do that to a lot of teams. With health on the side of Matt Schaub and Arian Foster and again with a solid defense, Houston could be the new kinks of the AFC South.
Tennessee: Jake Locker showed signs that he could be the quarter back of the future for the Titans but if Chris Johnson can't find his old form, it is going to be a tough year in Nashville.
Indianapolis: Andrew Luck played a lot better than people have given him credit for. Keep in mind, Luck is all the Colts have this year. Lets hope it gets better but I just don't see it.
Jacksonville: With MJD back, the Jags lost a heart breaker to the Vikings on Sunday. The most positive thing to come out of the loss? Blaine Gabbert actually looked like a quarter back. If Gabbert has turned a corner, a good year could be ahead of Jacksonville.
AFC West:
San Diego: What could be the last year of the Norv Turner era got off to a good start. The new acquisitions of Meachem, Royal, and Brown all played pretty well. Rookie Melvin Ingram was outstanding. Lets see how the weeks unfold before we get to excited.
Denver: Peyton Manning was the old Peyton Manning, which is not a shock no matter what people say. Thomas and Decker have adjusted well to Manning and his play calling. The defense turned it on when they needed too. This could be a great year t be a Bronco fan.
Kansas City: According to a lot of people, finishing the last season on a high was supposed to translate into Romeo Crennel leading the Chiefs back to the top of the AFC West and the playoffs. After Sunday though, it looks like the same old Chiefs.
Oakland: New owner + new GM + new coach = no difference. At least for Week 1.


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Thursday night at the Piedmont Tech Center for Advanced Manufacturing Piedmont Tech instructors and staff, ZF representatives, students and their families were all in attendance to present the latest class of apprentices in the ZF Apprenticeship Program.
Robbie Ellis, Apprenticeship Program Director for ZF began by explaining the recruiting process of the program and recognition of the 9 new apprentices that were accepted into the program out of 90 applicants.
Landon Adams, Elvis Fitz, Austin Francis , Bryson Vaughn, Bryson Patterson, and Jose Hernandez, all of Clinton High School; Antwan Clark, Jertavious Miller, and Mathew Sullivan, all of Laurens High School then signed letters of intent for their scholarships.
After an opportunity for pictures with family members each student received their ZF hat and back pack. It was very much like college signing day for athletes.
Michael Morris, Director of Human Resources for ZF addressed the students by telling them to look in their empty bags. He then told them that over 20 years of work at ZF they could put 8000 one hundred dollar bills in those bags.
These nine apprentices will begin New Hiring Orientation at ZF this coming Monday and begin classes at the CAM the following Monday.


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Posts Tagged 'weight loss'
Posted by: runawaynotes on August 21, 2012
"You ran today! You should totally be able to have that second cookie/third cheesecake slice/fourth martini…."
Posted by: runawaynotes on July 9, 2012
Posted by: runawaynotes on August 21, 2012
Posted by: runawaynotes on July 9, 2012
Thoughts on being human
Marathon / Half Marathon Training & Beginner Running Program
A site that brings the excitement of tax law and the joy of politics together.
Run long. Run hard. Run forever.
It's not sweat. It's sparkle.
Weight loss, fitness, insanity.
Just your average girl, with above average dreams and a not so average running life
Fighting for health in my life one run, meal, and choice at a time
The latest news on WordPress.com and the WordPress community.


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All purpose tissue oil.
Gentle and soothing action.
Body aligned, skin compatible botanical oils
Light, deep penetrating, residue free texture.
Minimises skin damage.
Excellent scalp treatment and hair regenerative.
Taryna Distressed Skin Complexes offer fast relief and intensive care for over sensitised and damaged skins. Powerful soothing and regenerative properties combined in these products instantly ease sensitivity, and simultaneously facilitate recovery, fast tracking healing processes and optimising the regeneration of healthy skin tissue.
Treat instances of inflammation and dehydration caused by overexposure to sun, wind and extreme temperature, abrasion, blistering, lesions, rosacea, wet and dry eczema and some occurrences of psoriasis. It also neutralises insect bites and balances PH and hormonal fluctuations in the skin. Anti microbial properties facilitate detoxification and the treatment of commonplace skin blemishes and breakouts, boils, acne and pimples, or localised bacterial infections.


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Make A Haunted Dollhouse For Halloween
We like our dollhouses here at Ohdeedoh. They delight little ones and give us grown ups a chance to "decorate" another home, albeit a dimunitive one. If you're putting up Fall and Halloween decorations in and around your real home, don't neglect the little house.
Gather some small-scale decorations (or make some) and have the kids turn the dollhouse into a haunted one. Or do as we saw on The Willows - buy an old dollhouse from a flea market (they got theirs for just $5) and haunt it. An old dollhouse maybe the better way to go as it can already look a bit spooky even without decoration. For more photos of this fun and frightening project, go and check out The Willows.
(Image: The Willows)


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As you've all probably heard, the Supreme Court of the United States recently declared gay marriage legal across the country, ruling state bans on equal marriage unconstitutional. The achievement of marriage equality in the U.S. is great news, and an important victory for the LGBTQ community. Gay couples are finally able to have their relationships recognized by the law, and the media has provided extensive coverage of their jubilant reaction since the decision was rendered at the end of June. At the same time, though, this type of coverage is a symptom of the widespread perception of marriage rights as the ultimate expression of LGBTQ equality, an approach that is blind to a host of other forms of discrimination aimed at the community.Trans people, for one, remain a target of extreme legal discrimination.
Mere months prior to the Supreme Court equal marriage decision, the Texas House of Representatives introduced a bill that would allow cisgender students to collect a fine of $2,000 from their school, if the school allows trans students to use the "wrong" bathroom. , This made Texas the fifth state to introduce this kind of transphobic legislation. Days later, Nevada introduced a similar bill to restrict trans students' access to washrooms and locker rooms that coincide with their gender identities. Trans people are often denied healthcare coverage and prohibited from changing their gender markers on official documents to reflect their gender identities. Here in Canada – which prides itself on having recognized equal marriage years prior to the U.S. – a proposed federal bill to include gender identity as a prohibited ground of discrimination was amended in the Senate to bar trans people from public washrooms. Trans people have been fighting for their rights just as loud and clear as marriage equality activists; often, they have been the ones left behind.
While some activists may believe that the work is done, it is not.
Now as ever, the LGBTQ community and activists must fight for the basic rights of trans people. The recent U.S. Supreme Court decision recognized a constitutional right for people "to define and express their identity" – like state bans on equal marriage, discriminatory measures aimed at trans people infringe on that right. This is no time to leave the battle behind, blinded by the taste of success; rather, now is the time to redouble our efforts.
Of course, in doing so, we should be mindful of the historical trans-exclusiveness of our own activisms. As a recent example, consider the advocacy organization Human Rights Campaign (HRC), which was a major player in the push for marriage equality in the U.S.. While many people changed their Facebook profile pictures to equality signs as part of an HRC campaign in 2013, most did not know about or acknowledge that HRC had come under fire for silencing trans activists in their ranks. Activist groups composed of mostly white gay men have had their disruptive demonstrations praised, while Jennicet Gutiérrez, a trans woman of colour, was criticized for her interruption of Barack Obama's recent White House Pride reception speech. This double standard cannot make for inclusive and effective activism.
While some activists may believe that the work is done, it is not. Trans people continue to face legal discrimination, and equal marriage activists owe the trans community their support. The LGBTQ community has a choice: will it amplify the voices of trans activists, or will it silence them?
Precilia Hanan is a 2nd year Psychology student. To reach her, please contact firstname.lastname@example.com.


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Sometimes Solar Cooking Ticks Me Off
Like all passions, sometimes you get so caught up in what you are doing, that you can lose your cool when things go awry. Many times this occurs when you forget something essential. Solar cooking isn't much different that way. If you have been solar cooking for awhile, you have probably adapted to much that will be mentioned here, but it doesn't mean you might get a little upset at yourself.
Like the song says, "Don't worry, be happy now"
Say, you left on a short road trip with your oven(s) and forgot an oven thermometer. That will get you stirred up! We rely on those little devices a lot. But, in most cases, you can overcome that if you have been solar cooking for some time. You have a fairly good idea about how long the food has to be in the cooker. Of course, you can always go by the physical manifestations; is the water/soup/chili, etc., boiling like it is supposed to? It's almost a no brainer if you are baking bread or a cake, just sample it, right?
Don't let some of the other things bother you either. For example, like forgetting a certain spice for the recipe; it will just turn out a little different, or, maybe add it after it is done cooking. Maybe you couldn't find your dark-colored metal pot, well, shiny ones still work, just not as well. Leave it in the sun a bit longer. You don't have to get ticked off about this stuff. Your next solar cooking experience will make up for it.
And, regarding Ticks, which are becoming more of an outdoor hazard just about anywhere, we have a solution. Try this tick repellent. Those little buggers are getting to be a real nuisance! Stay green!


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Anthony Mackie Rejoins Kathryn Bigelow For Detroit Riots Drama
Anthony Mackie was always a good actor but I don't think people truly took him seriously until he co-starred with Jeremy Renner in Kathryn Bigelow's Best Picture winner, The Hurt Locker. That set his career on a completely different trajectory, and of course we've seen him in a number of serious dramatic roles and as Falcon in the Marvel universe. Now as Bigelow puts together the ensemble for her Detroit riots film, Mackie has signed on to be a part of it.
Deadline reports Mackie has a role in the still-untitled drama centering on the racially charged riots that shook Detroit over five hot summer days in 1967. He joins John Boyega, Will Poulter, Ben O'Toole, Jack Reynor, and Hannah Murray in the film, playing a returning Vietnam veteran.
Filming begins soon in time for a release in 2017, the 50th anniversary of the riots.


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Giant Runaway Tire Mauls Unsuspecting Woman on Side of Road
Nothing good happens on the side of a highway. You can thank our friends in China for this important life lesson.
This woman was stretching on the shoulder of a highway when a giant tire that came loose from a truck barreled down the road and knocked her over a railing, causing three fractures and giving us the chance to make the lame joke that this shoulder should more accurately be called a broken shoulder.
Authorities say the woman and the driver of the truck that held the tire are both to blame.
But, back to the important stuff -- nothing good happens on the side of a highway. You're not meeting your soulmate there. You're not finding a million dollars just lying around there. Your website isn't going public while you're reading to the blind there.
If you're on the side of the road, odds are your car broke down, you've got to take a leak (and hopefully nothing more) or you're trying to find the perfect location to dump a body.
So, buckle up and don't get out until you see a sign for a rest stop where the worst thing that can happen is you're forced to pay $4 for a can of Dr Pepper to quench your thirst.


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- Artist: Andy & Denise
- Format: CD
- Release Date: 1/7/2003
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Andy & Denise are acoustic singer/songwriters who feature well crafted songs, compelling harmonies, and Andy's intricate guitar playing which often adds a 'third voice' to their songs. They are happy to announce the release of two new CD's: 'Covers' and Andy's solo acoustic instrumental CD 'The Long Walk Home'. These join their two previous releases 'Go' and 'Sunlight In Goodbye'. Andy & Denise are from the Philadelphia area and have been performing along the east coast for a number of years. They have played in coffeehouse series, house concerts, colleges and music festivals including The Minstrel Coffeehouse (NJ), Godfrey Daniel's (PA), 333 Coffeehouse (MD), Eddie's Attic (GA), The Point (PA), The Six String Cafe (NC), The Bluebird Cafe (TN), The Goodfolk Coffeehouse (CT), Moore Music in the House (MD), Delaware Friends of Folk Coffeehouse, the Brierfield Music Festival (AL), Delmarva Folk Festival (DE) and the Forksville Folk Festival (PA). Whatever the setting they are fun and engaging to watch! Andy Fox cut his teeth on the Boston music scene, playing in a number bands while attending Berklee College of Music. Denise O'Brien moved to New York to pursue acting and has performed in numerous commercials, soaps and theater. She has also created a line of handmade items under the label D'Pholk Crafts. Andy & Denise also run their own music recording studio called Gemini Squared Studios. Through their combined talents they are able to produce, record and mix music for other artists. Some of the projects they have produced are 'Engine' by We're About 9, 'God's Poet Now' by Erik Balkey, and 'Another Tourist' by Eliot Bronson. Andy Fox - vocals, acoustic guitar Denise O'Brien - vocals, acoustic bass 'Denise has one of those voices that sounds like she is smiling as she sings. Together, their equally strong voices often cross gender-defining pitch boundaries; a pleasant change that not all duos can handle. Listeners comfortable with David Wilcox and Eddie From Ohio will make familiar guitar and vocal connections.' -Angela Page, SingOut Magazine.


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These days every citizen of Delhi thinking about the Odd Even formulae of Delhi Government to control enormous amount of pollution in the national capital, Delhi. The pollution of Delhi has increase a lot in recent year. To find the solution of this, the government has announced that private vehicles bearing odd and even numbers will be allowed to ply only on alternate days. Cars having even number plate will play on even date that is 2, 4, 6 date while odd number cars will play on odd date. Only emergency vehicles such as PCR vans, fire tenders, and ambulances will be allowed to run on all days. Starting from new year for 15 days trail basis. This decision drew very quick response from the citizens of Delhi and across India. Here we are going to share some latest troll on odd and even number vehicle.
I personally support this decision of Delhi Government because extra ordinary problem requires extra ordinary solution.
Odd and Even number troll
Latest images of odd even number vehicle formulae of Delhi Government
source: hindustantimes
source: indian express
Latest Video on Delhi Governmet odd even formulae
Like this article on Odd and Even number trolls.


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Ms Natasha Ridge
Natasha Ridge is currently the Executive Director of the Sheikh Saud bin Saqr Al Qasimi Foundation for Policy Research. Prior to this, she was the Acting Director of Research at the Dubai School of Government. Natasha has a number of publications, including a book entitled Education and the Reverse Gender Divide in the Gulf States: Embracing the Global, Ignoring the Local. Her additional publications include chapters in the World Education Yearbook and in publications of the Emirates Centre for Strategic Studies and UNESCO as well as working papers for the Dubai School of Government and the Al Qasimi Foundation for Policy Research.
Natasha holds a doctorate of education in international education policy from Columbia University, and a master's in international and community development from Deakin University, Australia. She is also a founding board member and former president of the Gulf Comparative Education Society. Natasha's latest research focuses on the role and impact of Arab father involvement, philanthropy and education, and access and equity in the Gulf education sector.


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JM20336 USB2.0 to SATA Bridge Adapter eSATA Converter Cable for Sata Hard Drives
New Design with USB 2.0 and eSATA Port. True Hot-plug and Hot-Swap USB 2.0 Adapter with 2Amp Power Supply, Great Test Bench Device. Converter for SATA HDD, conect any SATA Device to your USB 2.0 Port! CHIPSET: Jmicron-JM20336 Single Chip Ultra Fast Solution USB 2.0 Adapter to any Native SATA 3.5 Drive from 80GB up to 2000GB(2TB). Compatible with Windows ME/2000/XP/2003/Vista.Works with MAC OS X.3.6 or Greater! Adapter plugs directly to your usb 2.0 port on a windows based computer and provides one SATA Signal/Power port to connect directly into your SATA 3.5inch or 2.5inch HDD.
Uses Jmicron Chip for Conversion. Tested with WD/Maxtor/Seagate/Hitachi SATA drives. Package includes Adapter cable and one DC 2AMP Power Adapter provides external power to your drive. USB2.0 to serial ATA translation. It includes the Jmicron Worlds First Single Chip SATA HDD to USB 2.0& Serial ATA PHY, Link, Transport. The Serial ATA physical, link, and transport layers are compliant to Serial ATA 1.0 , converter supports a SATA 1.5GHz and 3.0GHz data rate & USB2.0 480MHz data rate . The application layer supports both the ATA register command set and PACKET command set, which could drive SATA Hard Disk with LED Indicated power and Back-UP Software Button.
Support Win-98se,Win-98me need driver Support Win-2000,Win-xp free driver Easy install & free driver Max speed (Read + Write) : 48M Byte USB2.0 Specification compliant USB2.0 JMICRON 20337 newest chipset installed Serial ATA 1.0 Specification compliant Automatic Serial ATA 1.5/3.0 Gbps speed negotiation Support USB2.0 plug & play Support Serial ATA hot-plug Ultra low power consumption Work for both AC and DC couple between the transmitter and the receiver Provide specified OOB signal detection and transmission Support Spread Spectrum Clocking to reduce EMI Support Partial/Slumber power management Provide adjustable TX signal amplitude and pre-emphasis level
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|There he goes... Mr. Ikhlas and His Doggy Tales.
|Mr. Ikhlas would like to have a Husky breed one day.
I am not surprised, the Huskies look gorgeous.
|This is one reputed location for the Cave of the Sleepers, near Amman, Jordan.
Another location is in Ephesus, Turkey.
wa min Allah at-taufiq
Earlier Doggy Postings - Seven Reasons why Dogs are like Saints Click Here


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Friday, 23 November 2012
Reticulated Giraffe
10 comments:
- Sylvia K said...
What a terrific capture, JM!! I love the giraffe! What a beauty!! Hope all is well with you and your family! Have a wonderful weekend! Enjoy!!
- 23 November 2012 at 15:44
- Joop Zand said...
You show us always very nice photo's and places..... thanks for that.
Greetings and a nice weekend, Joop
- 23 November 2012 at 16:07
- Arija said...
What a wonderful scene. The giraffe looks looks a Japanese crazed glaze pottery.
- 23 November 2012 at 16:39
- Lowell said...
These are such funny creatures. We have a couple of them at the Silver Springs Park and they come over to the fence wanting to be fed. But if they get frustrated they spit at you and they smell absolutely awful! :-)
- 23 November 2012 at 17:51
What a great capture! They're such beautiful animals.
- 24 November 2012 at 00:26
- fotonita said...
Great capture! Beautiful colours!
Have a nice day!
- 24 November 2012 at 00:30
- Kathy said...
How wonderful that you got to photograph this exquisite creature in its native habitat. I've only had the pleasure of seeing them in zoos!
- 24 November 2012 at 01:50
- Food, Fun and Life in the Charente said...
It amazes me how different the markings are on these to the ones further South. Great shot. Diane
- 24 November 2012 at 14:05
- Red Angel said...
- 25 November 2012 at 18:16
- Stickup Artist said...
I love the markings or patterns. I wonder how those evolved (I must google that)? Looks like (s)he is just as curious about you as you are...
- 25 November 2012 at 18:40


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A magnet or engagement photo is a safe route to go when it comes to your save-the-date cards, but we recommend getting a little bit more creative since the invite-before-the-invite is your first opportunity to show guests who you are as a couple. The right wedding announcement also helps set the tone for your big day, whether you're throwing a black-tie affair or a backyard barbeque bash.
Save-the-dates serve another purpose besides just looking pretty: They're an essential part of wedding etiquette. You must give guests enough time to make travel arrangements — even if you're not hosting a destination wedding.
To help you find the right save-the-date, we recruited expert stationer Cheree Berry to decode ten unique options for any style of wedding. From a digital save-the-date that's way more sophisticated than an email blast to trendy ombré or laser-cut cards, these announcements are guaranteed to stand out in your guests' mail stacks. One of our favorites was the modern, typographical option shown above featuring a tucked-away shot from the couple's engagement session. It's romantic and sophisticated without reading overdone or cheesy.
See more of Berry's save-the-date picks by clicking the below link.
Click through to see what your save-the-date can say about you in the full slideshow!


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Being a Listener is a course designed by the Donegal Women's Centre.
It is intended as a follow-on for women who completed the 10-week "Introducing Women to Counselling & Listening Skills".
It may also be open to women who have done a similar course in basic introduction to counselling.
After completing Part 1 & 2, participants will have an opportunity to join our Listening Team.
Commencing: Tuesday 6th March 2018
Time: 10.00am – 12.30pm for 10 weeks
Tutor: Jacque Walsh
Cost: €40 / €20
To ensure your place is secure, course must be paid in full on or before Tuesday 27th February 2018
This course is part-funded by the Co. Donegal ETB Community Education Support Programme.
For further information or to book your place, please contact the Donegal Women's Centre, Port Road, Letterkenny on 074 9124985 or email email@example.com


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North Carolina is deep in the throes of another really hot, sticky summer, of the sort that makes you stay inside all day watching reruns and not caring that the lawn hasn't been mowed since April Fool's Day. I don't mind, because I'm not the one who does the yard work and when Jenda takes a nap, I get to watch grown up TV. Trust me, there are worse ways to spend a summer.
So between catching up on the soaps and enjoying marathon sessions of Designed to Sell on HGTV, I have realized that all of the soap opera families name their kids really weird shit, like 'Thorn', and 'Granite', and as far as home staging, mine is more like 'Designed from Hell', but I still like to watch these shows. Sometimes, you just have to live vicariously through television. With that said, while I enjoy TV, I am flabbergasted at the depths to which advertisers have sunk to peddle their products.
It's just a sad fact of TV watching that your show is going to be interrupted, frequently, by commercials. That leads to channel surfing by people like my husband and just dealing with it by lazy, er, patient people like me. So as I sat the other day waiting for whatever it was to come back on, I saw a commercial that gave me a worse case of the heebie-jeebies than that icky movie with that Leather Face guy and the chain saw. You might have seen this commercial. It's an advertisement for Burger King's new breakfast combo.
Picture it. The scene opens with a man in bed, just waking up as sunlight streams in the windows and birds sing outside. He yawns, stretches, rolls over and there is a GIANT, PLASTIC, BOBBLE-HEADED BURGER KING IN HIS BED!!! This is no lie! So this guy looks at this grotesque member of high-cholesterol kingliness, who proceeds to hand this hapless man a breakfast sandwich. The man takes a bite and then the two are laughing, having a manly breakfast moment. I have five words for this.
This is messed up on so many levels I hardly know where to begin. First, if there was some giant bobble-head in a crown in my bed with a sausage sandwich, I would start SCREAMING LIKE A BITCH!!! Then I would grab my rather heavy lamp off my nightstand and beat his bobbly ass to death. But then I started thinking more about the situation. Is the guy in the commercial a bachelor? If not, what happened to his spouse? How did His Highness get into the house? Why didn't the guy react?
Sadly, I think this guy did have a wife or significant other who was probably very health conscious, or perhaps was a vegetarian. I say 'was' because she's dead now. She had the good sense to freak out and not eat the breakfast sandwich and King Cholesterol killed her and turned her into a whopper combo meal. And then there's the question of how the king got in. I assume that the house had no alarm system, because if it did, it was a monumental failure. Can you imagine calling your home alarm company?
"Hey y'all, WTF? I JUST WOKE UP WITH SOME GIANT-ASS BOBBLY-HEADED BURGER KING IN MY BED AND MY ALARM NEVER WENT OFF!"
"Thank you for calling ABC alarms. Your call is important to us and will be answered in the order in which it was received. Your estimated wait can be measured in terms of geologic time. This is a recording…."
And finally, something is really wrong with newly single sleeper guy. I'm talking fundamentally flawed here. He had the fight or flight response of eye crud. I asked my husband Jerry what he would do in this situation. I frequently ask Jerry for advice. In my world, WWJD means 'What Would Jerry Do' and when I find out, I usually do the opposite. Or I just suggest that he go ahead and do it since, in telling me what he would do, he obviously has a plan. Anyway, he pondered the situation and then said, "I would go all Tony Soprano on him and beat him to death."
For once, we agreed. Sing with me, 'This magic moment….'
While I realize that the economy is in shambles and consumer confidence and spending are down, I don't think this marketing through fear is the right approach. This is not a commercial that makes me want to run out and buy the BK breakfast combo. It does, however, make me want to run out and buy a semi-automatic weapon. Did Burger King hire Machiavelli to come up with their new ad campaign?
"If it's better to be feared than loved, then let's scare the crap out of people to make them eat our food. No one wants to wake up next to a giant plastic burger mutant, so we'll send the unmistakable message that if they don't eat our food, we're coming for them! BWUHAHAHA!"
The commercial ends with King Creepy putting his hand on sleeper guy's knee, finally eliciting an alarmed reaction from him. Dude, why get upset now? He's in your bed, he gave you food, and he probably killed your wife. He's not leaving with just a handshake. The good old days of Have It Your Way are over. It's the BK way or the highway. That's when I had to go pluck out my own eyes and gargle with Drano. Well, no, but I vowed never to eat at Burger King ever again. That's a pretty healthy outcome for me. But I'll never look at Yul Brenner the same way again.
And I nailed all our windows shut.


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A Ford Mondeo which was stolen overnight from a residence in Maybole's Parkview was later recovered on the B7045 road to Kirkmichael.
The car was stolen from Parkview overnight on the 11th December.
Anyone with any information is asked to contact PC Emerson at Maybole police station on the non emergency 101 number.


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For more information contact CMU's Financial and Student Services Advisor.
Canadian students that enroll through CMU will pay all fees through CMU, and will receive in February the form T2202A (Tuition, Education, and Textbook Amounts Certificate) that can be used to claim federal and provincial non-refundable tax credits.
Each province uses different tax rates and the amount of credits you can claim based on your T2202A varies by province; prospective students should check their provincial tax forms to find out what amounts they would be able to claim.
Canadian students will also be eligible to apply for student loans. Student loan applications open in June for the fall and winter semesters. You must apply to the province of your permanent residence. Go to www.canada.ca/en/employment-social-development/services/student-financial-aid.html and follow the links to your province.
CMU students enrolled in one of the MA programs are invited to apply for one or more scholarships/bursaries. View the list of Graduate Studies scholarships and bursaries available. Most awards are granted in June, but in some cases there may be other scholarship or bursary money available that has not yet been assigned. Please contact the Financial and Student Services Advisor for more information.
Here are some helpful sites that give both information and help in searching for scholarships and awards. If you need help applying please contact the Student Financial Services Administrator.
If you are interested in on campus employment, go to www.cmu.ca/studentemployment to download an application form. Return the completed form to the Financial and Student Services Advisor in person or by email to student_employment:@:cmu.ca.


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Local businessman Frank Apa received Patch, a Shih Tzu, as a puppy. Patch was a sweet endearing little dog and when he began coming to work, he quickly became the company companion, mascot and spokes dog. As a canine ambassador he exemplified all the reasons why having animals in our lives has a positive impact.
Sadly, in August of 2002, Patch passed away. To honour his long time companion, Mr. Apa dedicated the month of September at the dealership. Over the month a donation was made from each car sale and the dealerships raised $13,300! The money was generously donated to the Oakville & Milton Humane Society in Patch's memory. This donation enabled the shelter to create the PATCH Challenge – a program which highlights the human-animal bond. Patch, the little dog's name has come to stand for People and Animals Together Create Harmony. Since then, Mr. Apa, President of Lexus of Oakville has continued to dedicate the month of August to support the kindness initiative and makes a substantial donation every year.
Through the Patch program we challenge students in our community to be kind to people and animals. We challenge teachers to bring the Oakville & Milton Humane Society into their classrooms. We will continue to recognize children in our community who demonstrate kindness to all living things. The PATCH Challenge is made possible through the generous donation of Mr. Apa and Lexus of Oakville.
Take The PATCH Challenge as part of your school's humane education program.
Learn why People and Animals Together Create Harmony.
Preschool Challenge – Ages: 3-4 years old
- Presentation: Approximately 30 minutes
Our programs for preschool children are interactive and fun. Children will learn about responsible pet ownership, safety around animals, and lending a helping hand. A small animal is brought to the school for the children to interact with.
Primary and Secondary children – Ages: 5-18 years old
Children will learn about responsible pet ownership, safety around animals, and lending a helping hand. A small animal is brought to the school for the children to interact with.
- Presentation: Approximately 30 minutes to 1 hour
Our programs follow the Ontario School Curriculum. Topics include: animal appreciation, responsible pet ownership, wildlife and habitats, pet overpopulation, animal cruelty, animal rights and the law, and much more. We will also design a presentation to suit your needs. An animal can also be requested to come to class for the children to interact with.
The PATCH Challenge program compliments the Ontario curriculum and delivers the following learning expectations for primary students:
- Effective communication
- Making sense of simple written materials
- Listening to stories and poetry
- Sorting and classifying objects
- Counting
- Demonstrating curiosity and care for the natural world
- Demonstrating an awareness of health and safety practices
- Demonstrating a positive attitude towards themselves and others


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We are glad to welcome a post of our first guest blogger, Cherie Enns. Cherie Enns is the coordinator of the project Eminus Academy, a program of the United Nations Human Settlements Programme (UN-Habitat), BASF Foundation and the University of the Fraser Valley (UVF). Eminus Academy is a close partner of Eliademy and offers courses on our platform.
Eminus achieving education for all
Eminus Goal:
To create an entrepreneurial and sustainable development applied certification program that is interactive and dynamic (in essence a virtual global classroom), using state of the art digital media[1].
Eminus is a program developed in collaboration with the United Nations Human Settlements Programme (UN-Habitat), BASF Foundation and the University of the Fraser Valley (UVF) based around the identified need for accessible education globally. With many young adults in developing countries having limited education and few employable skills Eminus focuses on skills development, entrepreneurship, sustainable development, and food security/agriculture. Through the lens of globally accessible intervention, Eminus addresses the need for linkages between education, skills, and employability, specifically for individuals in developing countries. This is something that UNICEF identifies as lacking in the global educational framework in their "Making Education a Priority in the Post-2014 Development Agenda[2]" report.
As outlined in the report, global themes were discussed at the High-Level Panel of Eminent Persons on the Post-2015 Development Agenda, including education. Within the thematic consultations, education was the prominent discussion, with equitable access, quality of learning, global citizenship, skills, and jobs, and governance and financing being key themes within the context of global education and outreach. As such, education is a priority theme of the 2015 Development Agenda. Within the dynamics of education, several gaps in the current educational framework have been highlighted, including lack of targeting for poor and marginalized communities and people, low priority for secondary or post-secondary education, and a lack of quality education that enables success in higher education. The narrow vision of access, with the focus on primary education, has proven inequitable to children living in poorer areas, and has led to a deficiency in prioritization of secondary, vocation, and tertiary education. Other shortcomings of the educational framework identified in UNESCO's consultations included gender equality and lack of investment in education. Gender equality has not been a reality within the global education framework, with over 1/3 of women between the ages of 15-24, in developing countries, not able to read; thirty-one million of the fifty-seven million children not in school are girls; and gender-based violence within schools presents a major challenge to girls' success and retention in school. The lack of monetary and political investment in education leads to a lack of access and quality of education in low-income countries.
In many ways, Eminus meets the suggestions for education improvements, promoting lifelong learning while improving the occupational mobility of young people. As an alternative to traditional education, e-learning and mobile education is more flexible and financially and globally accessible. Moreover, the program promotes gender equality, international learning, participatory learning and mentoring, within a post-secondary educational framework. Eminus ultimately aims to enable young adults for positive change. One student, said that "Through the Programme I was able to take my idea from mere concept to being one step closer to development by writing a Business Plan and creating a video pitch which would later be selected to receive seed funding from the UN-Habitat Urban Youth Fund Programme. Based on the current development of Link Your Purpose (LYP) I was able to apply for the prestigious Do School Social Enterprise Fellowship Programme in Germany…"
Students from over 30 different countries successfully completed one or more of the various courses. The diversity in international coverage of the program proved its global accessibility to young adults, reaching students mostly ranging in age between 20 and 35, in Cameroun, Egypt, India, Jamaica, Malawi, Rwanda, Senegal, South Sudan, Togo, Viet Nam, Zambia, and Kenya just to name a few. Thereby showing the potential and viability of such educational platforms in overcoming the current shortfalls of the global educational framework and ensuring education for even the most remote and marginalized individual.
To date, courses offered include Social Enterprise – A Tool for Sustainable Development; Community Mapping – Online Tools For Development; Seed to Market – Introduction to Urban Agriculture; Proposal, Partnerships, and Community Impact: Project Management and Beyond; all of which lead to development of social media, proposal writing, business entrepreneurship, financial reporting, community mapping, partnership building, and project evaluation skills and certification.
"This certificate is evidence of my experience and knowledge that I can use in my future." UN Youth Project in Afghanistan
The opportunities for growth within the program are as boundless as the World Wide Web with the opportunities for partnerships between education providers (universities, colleges, vocational institutes), technology providers (wireless providers, platform technicians, information technologies, mobility providers etc.), governmental and non-governmental organizations, private and public funders, becomes more available. Moreover, there is great potential in life-skills and business skills training, disaster training (such as Ebola response, flooding, draught, climate change etc.), peace building, cultural awareness, and language training that is contextual and diversified.
Eminus provides innovative learning opportunities and is proposed as a supplement to the traditional education system. It continues to grow and lead the way in outreach and connectivity, offering their students a chance to reach their own potential while also providing the global community the labour force that it has been lacking for so long. The opportunities that Eminus presents to young adults, communities, countries, and to the global market are dynamic and able to meet the needs of the current and future generations by its own adaptability and creativity. It is a tool that has long been required and will have profound effects on education globally for years to come.
[1] Eminus means 'at a distance' in Latin, branding of the program was designed by youth.
[2] http://www.unicef.org/education/files/Education_Thematic_Report_FINAL_v7_EN.pdf
Did you know it? Eliademy is a member of the United Nations Global Compact and strongly believe in the importance of Corporate Social Responsibility. If you want us to support your educational initiative send us an email at firstname.lastname@example.com


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Yummy food for hungry tummies
Playing, learning and making new friends is hungry work ? and that?s why we?ve worked extra hard to make sure your child is served a healthy, nutritious menu while in our care.
Delicious food all day long
We know that children thrive when they have full tummies, so the chef prepares carefully scheduled meals and snacks throughout the day, including:
- Breakfast
- Morning tea
- Hot lunch
- Afternoon tea
- Late snack
All our ingredients are sourced from fresh, local produce and carefully prepared to ensure that your child benefits from a healthy, balanced diet.
Download our menu (PDF)


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- Potential records are not being added to the national database, so the overall picture of what is where is wrong.
- I research the natural history of the species that I identify, and if I don't know what something is, I can't find out what it does.
- All species have loose or tight associations with other species and their habitat(s). I am missing opportunities to find out these associations, and hence my ability to add to our knowledge is reduced.
Basically, I am limiting my knowledge and I am limiting my ability to add to the greater knowledge. So I have decided to start sampling specimens. This will enable me to identify specimens beyond "a tachinid" or "a lesser cranefly". It's a logical progression, and hopefully it will add to your knowledge as well as mine.
On Friday I attended a beginner's course on spider identification. Spiders are an area that I have largely ignored for a number of reasons, and I think it's time to embrace them and begin to record them properly. The literature isn't cheap, but there are hundreds of species out there, and I'm sure I can make some progress in this very under-recorded group.
During the fieldwork we found this harvestman:
|The harvestman Platybunus triangularis
New to my species list.
The obvious oddity is the fact that the patterns on the two wings are different. The left wing is clearly a female wing (it has plenty of dark spots), but the right wing has only a faint, single spot. The wings of male Green-veined White can vary a little, but I have seen identically-marked males. So the question is: is this a gynandromorph (half female, half male)? Another thing to notice is that the abdomen is not straight: it has a distinct kink in it. This is a feature I have seen on images of confirmed gynandromorph specimens. The jury is out, but I'll report back later.
My first collected specimen is a Water-measurer - Hydrometra stagnorum:
Hydrometra stagnorum is a water-walking bug that can be seen in the company of other water-walking species, but it's a lot smaller (12 mm.) One notable feature is the very long head: this is thought to be used to reach food below the water surface.
This Green-veined White butterfly is rather interesting:
|Green-veined White butterfly
My first collected specimen is a Water-measurer - Hydrometra stagnorum:
|Water-measurer - Hydrometra stagnorum
New to my species list.


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Music First Festival Tickets
For more information about Music First Festival 0001 tickets, please visit the Music First Festival tickets page, part of our Festivals 0001 guide
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A two day music event to be held at The Oval in Hastings, East Sussex
Disabled Access Information
Disabled Attendee Information
Personal Assistant Ticket (PA)
If a customer is unable to attend the festival without the support from a PA, then we will provide an additional PA ticket at no extra cost.
The PA ticket is provided on the expectation that your PA is willing and able to assist you throughout your visit, and would be available and able to help you in the event of an evacuation.
This ticket can only be approved by the Access Team. Please do not buy a ticket for your PA as this will not be refunded if they are approved.
When applying for your PA ticket, please email one of the following to firstname.lastname@example.com
- DLA/PIP or equivalent
- Medical professionals letter
- D/deaf or blind registration
- Nimbus Access Card
It is mandatory to provide one of these forms of supporting documentation as evidence of your requirements. If you do not have the above evidence but feel you need assistance to access the festival, please contact us. Anyone turning up on the day without making prior arrangements may not be able to access our facilities. However, we will always try to accommodate any late requests.
Looking for something else? Find other festivals in November or try our new Festival Finder
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To see this year's full lineup, please use the link below
full Music First Festival 0001 line up »


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Centenarian claims hour record
Robert Marchand breaks the hour record in celebration of his 100th birthday
At the age of 14 he entered his first cycling event under a false name because he was too young: yesterday he established the first-ever best hour performance… in the category over 100 years.
And that pretty much sums up the personage of Robert Marchand. Full of energy and motivation, when he gets an idea in his head, nothing will stop him.
The centenarian rode 24.25 km (15.1 miles) in 60 minutes watched by crowds of cheering supporters at the International Cycling Union (UCI) velodrome in Aigle, Switzerland.
The feat does not threaten the 49.7 km (30.8 miles) achieved by Czech cyclist Ondrej Sosenka in 2005 at the age of 29, but it will be recognised by the UCI in a new over-100s category.
But I'm not playing at being a champion," he said. "I just wanted to do something for my 100th birthday."
With that intention in mind, less than three months after his birthday, he made the trip from his studio in Mitry-Mory (near Paris) to Switzerland to attempt the world hour performance on the center's velodrome. The suggestion that Marchand make the attempt came from Gérard Mistler, president of the Ardéchoise Cyclo-Promotion, an annual sportif event that Marchand never misses.
I think he is a human example of the benefits of cycling," said Mistler. "The fact that this performance is achieved at the WCC, headquarters of the International Cycling Union, is truly symbolic."
With Mistler taking care of the administrative side of this record attempt, the athlete himself was able to concentrate on his preparation, which included familiarizing himself with the center's track during the four days directly preceding the official date. While his ability to ride non-stop for an hour was not a concern, Marchand had to dig deep into his personal cycling history to retrieve the sensations of riding on the track.
"I haven't cycled on a track for 80 years. You have to get used to the fixed gear. I prefer cycling outside but that is impossible at the moment," he complained as he watched the snow fall heavily outside the WCC. "I don't want to catch the flu. So I am short on training."
His build-up at the WCC included a first initiation under the watchful eye and guidance of Magali Humbert, former junior world champion in the sprint and multiple French champion. The following days, he rode around the track accompanied by his "coach" Humbert, increasing his time in the saddle as the day of his challenge approached.
"The track is small. You just turn round and round," he commented after one of the training sessions. "I could keep going for another hour. I've been told not to raise my pulse too high so I'm not even tired."
For all his physical exploits, this man of small stature but big personality is obedient and follows medical advice. He has been told not to go raise his pulse over 110, and it is a rule he respects with reverence, for the most part. "I did climb a steep hill not long ago and went up to 134 but it's best to avoid that," he admits with a mischievous chuckle. "But I would be very surprised if I had heart attack," he offers spontaneously. Marchand's first ever cardiograph last week revealed that his heart was in excellent condition.
Optimism aside, he knows his limits and remains cautious. "For the last five years I have decided not to go for rides of more than 100km. There is no point going overboard. I want to keep cycling for some time yet."
These words of wisdom come from a man who last competed in the Bordeaux-Paris race at nearly 90 years of age, completing the 600km in 36 hours. In addition to filling sportif event results with his name, Marchand has a mountain pass named after him.
What is his secret? How is it possible to be in such frighteningly good physical, and mental, health at 100 years old?
"I've never abused anything. I don't smoke, I never drank much. The only thing I did in excess was work. I retired at 89 years old."
His many jobs include looking after cattle, his first job as a boy, his time as a gymnastics monitor with the Paris Fire Department, his eight years in Venezuela as a driver, his three years in Canada where he was a woodcutter. Then there are the myriad other sports he was involved in when he was younger: boxing, gymnastics (he was French champion in the pyramid as the lightweight at the top), weightlifting ("I was good," he explained. "I could have been a champion").
"I have to try to resume everything or we'll be here all night." It would certainly be worth staying up all night to listen to this man who has a memory that would put anyone to shame and stories to keep any audience captivated.
"But basically, I am like everybody," said Marchand. "I am lucky that I haven't had any major health problems. My advice to anyone, young or old, is to keep moving. I do 'physical culture' every day. It works out my whole body and keeps me supple. Some people when they reach 80 years old, start playing cards and they stay immobile. Not me. I've never been able to keep still." Clearly.