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Amyotrophic lateral sclerosis (ALS) is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development. The cysteine protease inhibitor cystatin C has recently gained interest as a candidate diagnostic biomarker for ALS, but further studies are required to fully characterize its biomarker utility. We used quantitative enzyme-linked immunosorbent assay (ELISA) to assess initial and longitudinal cerebrospinal fluid (CSF) and plasma cystatin C levels in 104 ALS patients and controls. Cystatin C levels in ALS patients were significantly elevated in plasma and reduced in CSF compared to healthy controls, but did not differ significantly from neurologic disease controls. In addition, the direction of longitudinal change in CSF cystatin C levels correlated to the rate of ALS disease progression, and initial CSF cystatin C levels were predictive of patient survival, suggesting that cystatin C may function as a surrogate marker of disease progression and survival. These data verify prior results for reduced cystatin C levels in the CSF of ALS patients, identify increased cystatin C levels in the plasma of ALS patients, and reveal correlations between CSF cystatin C levels to both ALS disease progression and patient survival.
Citation: Wilson ME, Boumaza I, Lacomis D, Bowser R (2010) Cystatin C: A Candidate Biomarker for Amyotrophic Lateral Sclerosis. PLoS ONE 5(12): e15133. doi:10.1371/journal.pone.0015133
Editor: Mel B. Feany, Brigham and Women's Hospital, Harvard Medical School, United States of America
Received: August 9, 2010; Accepted: October 22, 2010; Published: December 9, 2010
Copyright: © 2010 Wilson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Research funding was provided by the University of Pittsburgh Center for Amyotrophic Lateral Sclerosis (ALS) Research and NIH grant NS061867 to Robert Bowser. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have read the journal's policy and have the following conflicts: Robert Bowser is co-founder of Knopp Neurosciences, a biotechnology company devoted to the development of therapies for ALS and other neurologic diseases. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects approximately 1.5 to 2.5 per 100,000 individuals of all races and ethnicities throughout the world [1]. ALS patients typically undergo rapid disease progression, though a subset exhibits slow progression and may live over a decade from symptom onset [2], [3]. Unfortunately, there is only one drug currently approved by the FDA to treat ALS, and this therapy increases life span by just two to three months on average [4]. Clinical disease management is also hindered by an often lengthy diagnostic process based predominately on clinical criteria [5]. As new drugs that slow or arrest disease progression become available, early initiation of treatment will become paramount. For this reason, diagnostic biomarkers for ALS must be identified and validated to maximize treatment efficacy for future patients. Several individual panels of CSF proteins have shown promise as candidate biomarkers, but none have been fully validated or integrated into clinical practice [6], [7], [8].
Biomarkers also hold promise to monitor disease progression and to stratify patient populations for use in clinical trials. One reason new drug therapies have not been successfully translated from ALS model systems to humans is ALS disease heterogeneity [9]. Biomarkers that monitor disease progression would aid in the design and execution of human clinical trials and would provide novel targets for future drug therapies; prognostic biomarkers that predict patient survival would also aid in the design of clinical trials. While there are several validated demographic and clinical prognostic factors for ALS, disease prognosis cannot currently be predicted with high accuracy within individual patients [10]. Ultimately, surrogate biomarkers of disease progression would provide a means to more rapidly monitor drug efficacy in clinical trials [5], [9], [11], [12]. Therefore, the search for biomarkers that fit these functional characteristics represents a key challenge toward improving drug therapies and clinical management for ALS.
One protein that has shown potential for ALS diagnostic utility is cystatin C, a widely expressed cysteine protease inhibitor that is approximately five times more abundant in CSF than in plasma [13]. Cystatin C is processed through the secretory pathway, and, in its active monomeric form, inhibits a wide variety of cysteine proteases including cathepsins B, H, L, and S, calpains and caspases [14]. Cystatin C is also linked to ALS histopathologically, as it is one of only two known proteins that localize to Bunina bodies, which are small intraneuronal inclusions specific to ALS [15].
Two prior surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) studies reported significant decreases in CSF cystatin C levels in ALS patients relative to healthy controls [6] and mixed healthy/neurologic disease controls [7]. A recent study using small numbers of test subjects reported a significant reduction in CSF cystatin C concentration in ALS patients relative to individuals with polyneuropathy, as measured by ELISA [16]. While these prior studies are encouraging, a larger study with a more comprehensive group of ALS-mimic disease controls is required in order to verify prior results and determine if CSF cystatin C levels represent a candidate diagnostic biomarker for ALS.
The objective of this study was to use quantitative ELISA to further evaluate the utility of cystatin C as a biomarker for ALS using a large subject population. Our subject group size was based on power analysis of previously published mass spectrometry reports on cystatin C in ALS [6], [7]. We evaluated cystatin C in both CSF and plasma as a candidate diagnostic biomarker, and correlated levels to individual ALS patient survival and disease progression. We verified that cystatin C protein levels are reduced in the CSF of ALS patients and discovered that cystatin C levels are increased in the plasma of ALS patients. However, cystatin C levels in either biofluid were not highly predictive of ALS. We also determined that CSF cystatin C levels correlate to ALS patient survival, and change during disease progression.
We collected longitudinal CSF and plasma samples from 104 ALS and control subjects (Table 1) and evaluated the absolute cystatin C concentrations by ELISA and the total sample protein concentrations by BCA protein assay. We then assessed the biomarker utility of two separate measures of cystatin C: (1) the absolute cystatin C concentrations or "total cystatin C" and (2) the "percent cystatin C," in which the absolute cystatin C concentrations were normalized to the total sample protein concentrations to determine the percent of total biofluid protein accounted for by cystatin C. We also collected several clinical measures of disease progression at the time of each biofluid draw (see methods).
Diagnostic biomarker assessment
In order to assess the diagnostic utility of cystatin C, we first compared the mean first-draw cystatin C levels among ALS patients, neurologic disease controls, and healthy controls. A generalized linear model was used to estimate the mean total and percent cystatin C for each diagnostic category, with both gender and age included as co-factors in the model. This statistical design controls for between-group differences in each co-factor when generating estimated means. Therefore, the differences in age and gender among our diagnostic groups should not have affected our results, even in the case that cystatin C varies with these factors. We found that the estimated means for both measures of cystatin C were lower in ALS patients than in disease controls and healthy controls, similar to prior studies (Table 2). However, a test of the model's main effects revealed that only percent cystatin C differed significantly by disease diagnosis, while total cystatin C levels were not significantly different across diagnostic groups. Neither measure of cystatin C differed significantly by age or gender. In a post-hoc pairwise comparison of diagnostic groups, percent cystatin C was found to be significantly lower in CSF of both ALS patients and disease controls relative to healthy controls, but there was no statistical difference between cystatin C levels in ALS patients and disease controls.
Next, we repeated these statistical analyses using data from specific patient subgroups, in order to determine if either measure of CSF cystatin C can be used to differentiate ALS patients from disease controls in specific patient subpopulations. First, we created a subcategory of disease controls comprised of patients with neurologic diseases that more closely resemble ALS at presentation. Using this group of ALS mimics in our statistical model, the patterns of overall and between-group statistical differences remained the same (data not shown). However, the p-values were reduced for the ALS vs. mimic disease control subgroup comparison (Table 3, first row) relative to the ALS vs. all disease control subgroup comparison (Table 2, "ALS vs. DC") suggesting a stronger trend toward statistical significance when cystatin C is used to differentiate ALS patients from this more clinically-relevant control group.
We next compared two ALS subgroups to the disease mimic group. Limb-onset ALS (ALS-L) and ALS patients greater than one year from symptom onset both exhibited reduced levels of cystatin C in the CSF when compared to disease mimics (Table 3), with improved p-values when compared to the analysis including all ALS patients. However, the pair-wise comparisons between these ALS subgroups and mimic disease controls still fell short of statistical significance.
Finally, we calculated the diagnostic sensitivity and specificity for several cutoff concentration values of CSF cystatin C. Total cystatin C concentration measurements were found to have better diagnostic parameters than percent cystatin C values. A cutoff value of 2.20 µg/ml identified a small subset of ALS patients (sensitivity: 23%) with relatively high specificity (88% vs. all study controls, 100% vs. mimic disease controls). A cutoff value of 2.70 µg/ml identified a modest subset of ALS patients (sensitivity: 32%) while maintaining high specificity versus controls (specificity: 78% vs. all study controls, 100% vs. mimic disease controls). A less conservative cutoff value of 3.50 µg/ml identified a majority of ALS patients (sensitivity: 52%), but demonstrated lower specificity (specificity: 52% vs. all study controls, 89% vs. mimic disease controls).
As noted above, cystatin C was previously reported to be significantly reduced in the CSF of ALS patients using mass spectrometry-based proteomics, but the between-group differences based on our ELISA data were less robust. To explore the relationship between CSF cystatin C levels measured by these two techniques, we compared our ELISA results with SELDI-TOF-MS data for the same CSF samples. We found significant, positive correlations between the 13.3 kDa SELDI-TOF-MS mass peak intensity for cystatin C and both total cystatin C and percent cystatin C protein levels as measured by ELISA (p = 0.002 and p<0.001, respectively; Figure S1). However, the correlation coefficients (Spearman r = 0.443 and 0.595, respectively) suggest that these techniques may be differentially sensitive to various modified forms of native cystatin C.
We repeated the group analysis for the diagnostic utility of cystatin C in plasma, and both measures of cystatin C varied significantly by diagnosis and age, but not by gender (Table 4). Post-hoc analyses revealed that total and percent cystatin C were significantly increased in both ALS patients and disease controls relative to healthy controls. However, there were no differences in cystatin C levels between ALS patients and disease controls. Identical trends were observed for all subgroup analyses of cystatin C levels in plasma (data not shown).
To further characterize the relationship between CSF and plasma cystatin C levels, we assessed the correlation between CSF and plasma cystatin C levels for individual subjects. The results indicated that there is no correlation between total cystatin C concentrations (Spearman r = 0.055; p = 0.626) or percent cystatin C levels (Spearman r = −0.076; p = 0.501) in CSF and plasma samples drawn from individual patients on the same day (Figure S2). The absence of a relationship between CSF and plasma cystatin C levels suggests that this protein is independently regulated in both biofluid pools, and that plasma cystatin C is unlikely to be directly influenced by CSF levels.
Cystatin C as a biomarker for disease progression
We next examined whether cystatin C levels change over time in ALS patients, and if these changes are associated with clinical disease progression. We compiled the first CSF draws for each of the ALS patients in our study and carried out linear regressions comparing both total and percent cystatin C with the time from symptom onset. Similar to a prior study [16], we found no statistically significant linear relationship between these variables in our data set (Figure 1). However, we did observe a slight trend toward a reduction in cystatin C levels over time from symptom onset, particularly for percent cystatin C (Figure 1B).
The slope of the best-fit lines (solid) for both total (A) and percent (B) cystatin C did not significantly differ from zero (p = 0.368 and p = 0.193, respectively). Dashed line = 95% confidence interval for best-fit line.
Next, we collected longitudinal CSF samples from ALS patients and assessed the effect of time on cystatin C levels using a statistical model for repeated measures. This experimental design controls for individual differences in baseline cystatin C levels, but not for individual differences in rate of disease progression. We collected at least three longitudinal CSF draws from 15 ALS patients over a 1–2 year time period for each patient. When all 15 values were averaged for each time point, we did not observe a significant change in cystatin C levels over time (Table 5, "All Patients").
To control for individual differences in disease progression speed, we separated ALS patients into two groups: fast progressors, who demonstrated a rapid clinical decline during the study period, and slow progressors, whose clinical decline was slower than average (see methods section). When the rate of disease progression was included as a factor in the statistical model, we found a significant interaction between the effects of time and progression speed for total cystatin C measurements (Table 5, Time*Progression Speed column), indicating that longitudinal changes in cystatin C concentration follow different patterns in the two patient subpopulations. In order to determine the direction and significance level of the longitudinal subgroup changes responsible for this interaction, we applied the repeated measures test individually to each patient subgroup. Fast progressors exhibited a subtle, non-significant decrease in cystatin C levels over time. In contrast, slow progressors exhibited a trend of increasing cystatin C levels over time (p = 0.058, Table 5), which likely accounts for the majority of the time/progression speed interaction. Similar trends were observed for percent cystatin C measurements. For comparison, we also assessed the longitudinal change in CSF cystatin C levels in 10 healthy controls, each with two CSF samples drawn 1.5–2 years apart. A repeated measures t-test revealed a modest increase in total cystatin C concentration over time in these healthy controls but no longitudinal change in percent cystatin C levels (data not shown).
Correlation of cystatin C to survival
Finally, we assessed the relationship between first-draw cystatin C levels (in CSF and plasma) and patient survival time. Neither measure of plasma cystatin C showed a correlation with subsequent survival time (total cystatin C: Spearman r = −0.17, p = 0.537), but both measures of CSF cystatin C levels showed a direct correlation, with the results for total cystatin C almost reaching statistical significance (total cystatin C: Spearman r = 0.465, p = 0.052). These findings suggest that cystatin C levels in CSF but not plasma may be useful as prognostic indicators of patient survival time.
We further explored this correlation by generating Kaplan-Meier survival curves for total CSF cystatin C measurements. For these analyses, patients were sorted into high- and low-cystatin C groups according to their first-draw cystatin C levels. Qualitative data assessment revealed that short survival times were most strongly associated with the lowest cystatin C levels and, for this reason, we selected a cut-off value of 2.75 µg/ml to separate the ALS patients into a smaller low cystatin C group (n = 11) and a larger high cystatin C group (n = 21). This analysis revealed significantly longer patient survival in the high cystatin C group than in the low cystatin C group (Figure 2A). Next, because the ALS disease course and average survival time differ significantly between limb-onset ALS and bulbar-onset ALS, we repeated these statistical tests with exclusively limb-onset patients. Within this population, the between-group difference in post-draw survival time became even more striking (Figure 2B), further reinforcing our finding that ALS patients with low CSF cystatin C levels exhibit reduced survival times relative to patients with average to high CSF cystatin C levels. Similar results were obtained using percent cystatin C measurements.
For all ALS patients (A), survival was significantly longer (p<0.014) in patients with high cystatin C levels (n = 21) than in patients with low cystatin C levels (n = 11). For patients with limb onset ALS (B), the same trend was observed, but with a larger survival difference (p<0.010) between patients with high (n = 13) and low (n = 10) cystatin C levels.
The present study represents a comprehensive evaluation of cystatin C as a candidate biomarker in ALS, and is unique in its assessment of two distinct biofluids (CSF and blood plasma), two different measurements of the protein of interest (total concentration and percent of total protein), and longitudinally collected CSF samples. Prior studies using SELDI-TOF-MS found significantly lower cystatin C abundance in the CSF of ALS patients relative to healthy controls [6] and mixed healthy/neurologic disease controls [7]. These findings were validated by ELISA and immunoblot, respectively. In our current ELISA study for diagnostic utility using a much larger number of total subjects, we also found a significant reduction in cystatin C levels in the CSF of ALS patients relative to healthy controls, but the magnitude of this difference was less robust than in the previous reports. This discrepancy may have resulted from the use of different experimental techniques, as SELDI-TOF-MS recognizes discrete mass-to-charge forms of cystatin C, whereas ELISA may recognize multiple modified or cleaved forms of cystatin C depending upon the antibodies used for capture and detection. Regarding the comparison of these two techniques, we found a significant, positive correlation but a low correlation coefficient between our CSF ELISA data and SELDI-TOF-MS data for the same samples (Figure S1). This finding suggests that these techniques are sensitive to different, but possibly overlapping, ranges of native cystatin C isoforms, and may provide differential, and perhaps complementary, utility in detecting cystatin C for biomarker assessment.
To be clinically useful as a diagnostic biomarker, cystatin C must also be able to differentiate between ALS patients and individuals with neurologic diseases that closely resemble ALS, or ALS "mimic diseases." A recent study reported a significant reduction in CSF cystatin C levels in ALS patients relative to polyneuropathy patients [16]. In our ELISA analysis, cystatin C was reduced in the CSF of ALS patients relative to all DC combined and, to a greater degree, relative to a mimic disease control group that included a variety of ALS mimics (Table 3), but neither difference reached statistical significance. Because these between-group differences were smaller than we expected based on previous mass spectrometry data [17], we conducted a new power analysis using our experimentally-derived group means and standard deviations. This analysis revealed that our study was adequately powered for comparing percent cystatin C between ALS and HC (a significant difference was found), and underpowered for comparing total cystatin C between ALS and HC (main group effects missed significance, but the pairwise comparison was significant), and for comparing ALS with DC for both measures of cystatin C (no significant differences were identified). The observed reductions in both total and percent cystatin C in ALS patients relative to DC may reflect actual differences in clinical cystatin C levels, but a total study enrollment of 1020 and 675 patients (for total and percent cystatin C, respectively) would be required to confirm statistical significance with 80% power and 95% confidence. Interestingly, the between-group differences and trend towards significance improved when comparing limb-onset ALS patients or ALS patients with disease course greater than 1 year from symptom onset to the ALS mimics (Table 3). Additionally, we found that the total cystatin C concentration measurement generated superior diagnostic accuracy, indicating that this may be the more efficacious measure of cystatin C. An assessment of the diagnostic parameters of CSF cystatin C concentration revealed that the sensitivity of cystatin C for differentiating ALS patients from disease controls is low for all cutoff values but it displays high levels of specificity and, therefore, cystatin C can only identify a small subset of ALS patients. Together, these findings indicate that CSF cystatin C levels may differ between ALS patients and relevant disease control populations but cystatin C, by itself, has limited diagnostic utility. However, this protein could potentially improve the sensitivity and/or specificity of a diagnostic biomarker panel. Due to the heterogeneous nature of the ALS patient population, it is likely that a multiple biomarker panel will be required, as opposed to any single protein biomarker, in order to differentiate ALS from related disorders with adequate diagnostic certainty [18].
We also assessed the diagnostic utility of plasma cystatin C levels. Plasma cystatin C has been extensively characterized as a peripheral biomarker for kidney function and as a prognostic indicator of the risk of morbidity and mortality relating to cardiovascular disease [19], [20]. However, blood-borne levels of cystatin C have not been evaluated as a biomarker candidate for neurologic disorders. We found that plasma cystatin C levels are equivalently elevated in both ALS patients and disease controls relative to healthy controls, indicating that elevated plasma cystatin C is a nonspecific finding associated with neurologic disease states. Therefore, plasma cystatin C levels, as evaluated by ELISA, do not to have diagnostic utility for ALS. Furthermore, the absence of a relationship between cystatin C levels in concurrently-drawn CSF and plasma samples from individual patients in this study (Figure S2) suggests that this protein is independently regulated in each biofluid. Accordingly, plasma cystatin C levels are unlikely to be directly correlated with motor neuron degeneration in ALS, though elevated levels may correlate to peripheral metabolic or inflammatory abnormalities during ALS.
A recent study examined a single CSF draw per ALS patient, taken at varying times from symptom onset, to indirectly infer the average longitudinal change in cystatin C concentration in the group as a whole, and they reported that cystatin C levels do not change over time [16]. We completed a similar analysis and also found no evidence for a patterned directional change in CSF cystatin C levels over time in ALS patients (Figure 1). However, both heterogeneity in disease progression speed and individual variation in baseline cystatin C levels could mask significant trends in cystatin C change over the course of disease progression and, therefore, single-draw protein levels are unsuitable for a thorough assessment of longitudinal trends in cystatin C abundance.
We also examined longitudinal CSF data from multiple patients to more accurately assess the changes in cystatin C over time. We found that longitudinal cystatin C concentrations were relatively constant in ALS patients as a combined group. In contrast, the subgroup of patients with slow or absent clinical disease progression exhibited longitudinal increases in cystatin C concentration, and the subgroup with more typical, continuous clinical deterioration exhibited longitudinal decreases in total cystatin C. Interestingly, slow progressors often exhibited lower initial levels of CSF cystatin C than fast progressors (Table 5). Similar trends were also observed for percent cystatin C measurements, but statistical significance was not reached. These results indicate that CSF cystatin C levels in ALS patients change over time in a clinically-relevant manner and that increasing cystatin C concentration may be associated with slower disease progression. Conversely, rapid disease progression may be associated with a decrease in cystatin C concentration over time.
We also conducted an analysis to determine the relationship between longitudinal changes in CSF cystatin C levels and time-matched changes in three functional clinical measures of disease progression (ALSFRS-R, MMT, and FVC). However, no significant correlations were found (data not shown). This indicates that cystatin C levels may change independently of the clinical parameters used for monitoring disease progression. However, this finding does not eliminate the possibility that changes in CSF cystatin C levels correlate with more subtle biochemical changes associated with disease progression, as these may not be accurately reflected by overt functional measures of clinical disease status [9], [11]. Furthermore, the observed trend of increasing cystatin C levels in patients with slow rates of clinical deterioration may prove to be useful as an objective biomarker for monitoring drug effects in clinical trials.
We recently demonstrated a correlation between CSF cystatin C levels and patient survival by SELDI-TOF-MS [17]. In this study, we further verified a direct correlation between CSF cystatin C concentration and patient survival time, supporting the potential utility of this protein for prognostic applications. Subsequent Kaplan-Meier survival analyses for patient groups with CSF cystatin C concentrations above and below qualitatively selected cut-off values confirmed significantly longer survival times for patients in the higher cystatin C groups. Additionally, the prognostic capacity of CSF cystatin C was higher for limb-onset patients (Figure 2B) than for all patients combined (Figure 2A). This may have resulted from the confounding effects of combining patients with different sites of disease onset, as bulbar-onset ALS patients typically have shorter survival times than limb-onset patients [2], [3]. Unfortunately, there were inadequate numbers of bulbar-, trunk-, and/or dementia-onset patients to analyze these individual subgroups in this study, and further analyses are required to determine the prognostic capacity of cystatin C in these subgroups. Nonetheless, these results show that cystatin C is a candidate prognostic indicator of survival in ALS patients. Alternatively, cystatin C levels could contribute to the process of balancing prognostic variables among experimental groups as recommended to equalize drop-out rates and preserve the balancing effects of randomization in clinical trials [9]. Further work is required to more fully characterize the relationship between CSF cystatin C concentration and ALS patient survival, and to determine optimal cut-off values and procedures to stratify patients for prognostic purposes.
The results of this comprehensive biomarker assessment also have implications for the potential mechanistic involvement of cystatin C in the pathogenesis of ALS. The function of cystatin C within the CNS has not been extensively studied, but it appears to have both neurotoxic and neuroprotective properties [21], [22], [23], [24], though its effects specifically on motor neurons have not been reported. The majority of cystatin C in the CSF is produced by the choroid plexus [25], but it is unclear whether the apparent reductions in CSF levels in ALS patients are an independent etiological factor contributing to motor neuron degeneration, a downstream result of disease pathogenesis, or a compensatory response to ALS pathology. However, the association of higher cystatin C concentrations with longer patient survival and the association of increasing cystatin C levels with slower clinical progression both suggest that extracellular cystatin C may exhibit neuroprotective properties within the context of ALS. This would implicate any absolute or relative cystatin C deficiency in ALS as both a potential contributor to disease pathogenesis and a potential therapeutic target. Continuing work in our laboratory is focused on determining the effects of altered cystatin C concentration/activity on motor neurons in vitro, in order to clarify its potential mechanistic role in ALS pathogenesis.
In summary, we have completed a comprehensive evaluation of cystatin C as a candidate ALS biomarker, including assessments of two complementary measures of cystatin C in two distinct biofluids as well as examinations of both longitudinal CSF samples and patient survival data. Our findings indicate that cystatin C levels, as determined by ELISA, are increased in the plasma and decreased in the CSF of ALS patients relative to healthy controls. CSF cystatin C measurements may possess a more limited diagnostic capacity for ALS than previously proposed, but may still have the potential to improve the diagnostic parameters of a biomarker panel. Additionally, longitudinal changes in CSF cystatin C levels may be useful as a biomarker of fast versus slow rates of disease progression. Our data also demonstrate that CSF cystatin C concentration has prognostic utility in estimating patient survival time. Further validation studies are necessary to confirm these findings and ultimately determine if cystatin C measurements can be used to enhance clinical disease management and clinical trial design. Finally, the association of high or increasing cystatin C levels with slower disease progression and increased survival time suggests a potential neuroprotective role for this protein in the pathobiology of ALS.
Materials and Methods
Sample Collection and Ethics Statement
This study was approved by the institutional review board (IRB) at the University of Pittsburgh, and written informed consent was obtained from all participating subjects. ALS subjects were diagnosed by experienced neurologists specialized in motor neuron disease, using revised El Escorial criteria [26]. CSF and plasma samples were collected at the same office visit every four to six months from 44 ALS patients (2–8 draws), and either once or twice (1.5–2 years apart) from 35 non-neurologic healthy controls (HC) and 25 neurologic disease controls (DC). Our total enrollment of 104 patients provided adequate power for this study as a pre-study power analysis using projected effect sizes based on previous mass spectrometry findings [17] concluded that a total enrollment of 96 patients was required to identify pairwise differences between ALS patients and both HC and DC groups for both measures of cystatin C. We did not control for potential confounding variables such as socioeconomic status, nutrition, environmental exposures, etc. between diagnostic groups. The median time from symptom onset to first draw for ALS patients was 468 days. Clinical parameters used to monitor ALS disease progression included the rate of change in the revised ALS functional rating scale (ALSFRS-R), manual muscle strength tests (MMT), and forced vital capacity (FVC) [27], [28], [29].
The disease control group included six patients with multiple sclerosis, one with bilateral facial palsies, one with neurosarcoidosis, one with viral encephalitis, one with CNS lymphoma, one with brain metastases, one with pseudotumor cerebri, one with a seizure disorder, one with complicated migraine, one with paresthesis and possible myelopathy, one with a probable conversion disorder, and nine with neurologic diseases that can clinically resemble ALS at presentation. This ALS-mimic disease subgroup included two patients with primary lateral sclerosis (PLS), two with chronic inflammatory demyelinating polyneuropathy (CIDP), two with progressive muscular atrophy, one with spinocerebellar ataxia, one with small fiber neuropathy, and one with idiopathic sensorimotor polyneuropathy. CSF samples were obtained by lumbar puncture, immediately centrifuged at 450 g for five minutes at 4°C to remove cells and debris, aliquoted, and then frozen at −80°C. Intravenous blood samples were collected in EDTA containing tubes, inverted to mix, and centrifuged at 1,733 g for 10 min at 4°C. The plasma was decanted, aliquoted, and frozen at −80°C. CSF and plasma were aliquoted into small volumes for single use in experiments in order to eliminate any freeze/thaw effects. Samples of either biofluid were thawed on ice immediately prior to use.
Cystatin C ELISA
CSF and plasma samples from individual patients were assigned to random 96-well plate positions, and evaluated in duplicate wells for each ELISA. All samples were independently assayed at least twice. For all experiments, we used a human cystatin C sandwich ELISA kit (Biovendor, Candler, NC), according to the manufacturer's instructions. Briefly, diluted CSF and plasma samples (1∶2000 and 1∶400, respectively in dilution buffer) were applied to antibody pre-coated ELISA plates for 30 min with gentle agitation. The wells were washed thoroughly and then the secondary antibody conjugate solution was applied for 30 min with gentle agitation. After a second wash, the 3,3′,5,5′ Tetramethylbenzidine substrate solution (Biovendor, Candler, NC) was applied for 10 min, color development was stopped with an acidic stop solution, and the optical density was measured at 450 nm using a plate reader. Total protein concentrations for each sample were calculated using a BCA protein assay (Pierce), according to the manufacturer's instructions.
Data Processing.
For each ELISA plate, a standard curve was generated by plotting the logarithm of the cystatin C concentration against the logit log of the adjusted optical density (divided by a constant to produce a data range between zero and one, as required for the logit logarithm function). This procedure produced a linear standard curve, which was then used to calculate sample cystatin C concentration from sample optical density. The data points were averaged to determine the absolute cystatin C concentration, or "total cystatin C," for each sample. Sample cystatin C concentrations were normalized to the sample total protein concentration to determine the percent of total biofluid protein accounted for by cystatin C, or "percent cystatin C."
Assessment of Diagnostic Biomarker Utility.
For the analyses of diagnostic utility, we included only the initial sample collected from each patient, representing the time point closest to symptom onset. Differences between group and subgroup means were identified using the SPSS generalized linear model, with diagnosis and sex as factors in the model and age at draw as a covariate. This model was subsequently used to calculate and compare the estimated marginal group means, in order to determine which pairwise differences among the levels of each factor were responsible for the significant main effects.
Assessment of Longitudinal Change in Cystatin C.
The relationship between first-draw cystatin C levels and the length of time from symptom onset was assessed by linear regression using GraphPad Prism 5.0 software (GraphPad Software Inc, La Jolla, CA). For this analysis, the "time from symptom onset" data were transformed by the natural logarithm (Ln) in order to achieve normality as required by the selected statistical test.
The effect of time on longitudinal cystatin C levels in ALS patients with multiple biofluid draws was assessed with SPSS software, using the general linear model for repeated measures. The model was applied for all patients combined and for patient subgroups sorted by progression speed. Fast progressors were defined as patients exhibiting above average rates of ALSFRS decline (median: 0.77 units/month [30]) or MMT decline (mean: drop of 1%/month [29]), and slow progressors were defined as patients exhibiting smaller than average longitudinal decreases in both of these clinical progression measures.
The longitudinal relationship between cystatin C levels and clinical disease progression in individual patients was assessed by nonparametric correlation analysis (GraphPad Prism 5.0). The Spearman's rank correlation coefficient (r) was calculated and the permutation test was applied to determine if r was significantly different from zero.
Assessment of Prognostic Biomarker Utility.
The relationship between first-draw cystatin C levels and post-draw survival time (for deceased patients only) was assessed by Spearman correlation analysis (GraphPad Prism 5.0). The prognostic utility of CSF cystatin C was further explored by generating Kaplan-Meier survival curves for patients falling above or below several cut-off values of cystatin C. SPSS software was used to calculate the p-values for differential survival time by three different methods: the Log Rank (Mantel-Cox) test, the Breslow (Generalized Wilcoxon) test, and the Tarone-Ware test. For all statistical analyses in this study, the significance level was set at p<0.05.
Supporting Information
Figure S1.
Correlation of ELISA-based cystatin C levels and SELDI-TOF-MS 13.3 kDa mass peak intensity levels by Spearman correlation analysis. Both total (A) and percent (B) cystatin C ELISA measurements correlated to the 13.3 kDa cystatin C mass peak.
Figure S2.
Correlation analysis for cystatin C levels in CSF and plasma. There was no correlation between total cystatin C concentrations (A) (r = 0.055; p = 0.626) or percent cystatin C levels (B) (r = -0.076; p = 0.501) between CSF and plasma.
We would like to gratefully thank all the participating ALS patients and other research subjects for their generous contribution to this study. We also thank the University of Pittsburgh Clinical and Translational Science Institute for their assistance with statistical analysis.
Author Contributions
Conceived and designed the experiments: RB MEW DL. Performed the experiments: IB MEW. Analyzed the data: MEW RB. Contributed reagents/materials/analysis tools: DL. Wrote the paper: MEW RB. Enrolled patients and collected biofluid samples: DL. Edited and revised manuscript: DL IB.
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- 7. Ranganathan S, Williams E, Ganchev P, Gopalakrishnan V, Lacomis D, et al. (2005) Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. J Neurochem 95: 1461–1471.
- 8. Mitchell RM, Freeman WM, Randazzo WT, Stephens HE, Beard JL, et al. (2009) A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology 72: 14–19.
- 9. DiBernardo AB, Cudkowicz ME (2006) Translating preclinical insights into effective human trials in ALS. Biochim Biophys Acta 1762: 1139–1149.
- 10. Chio A, Logroscino G, Hardiman O, Swingler R, Mitchell D, et al. (2009) Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler 10: 310–323.
- 11. Bowser R, Cudkowicz M, Kaddurah-Daouk R (2006) Biomarkers for amyotrophic lateral sclerosis. Expert Rev Mol Diagn 6: 387–398.
- 12. Wagner KR (2009) The need for biomarkers in amyotrophic lateral sclerosis drug development. Neurology 72: 11–12.
- 13. George PM, Sheat JM (1989) Cystatin C quantification in CSF. Clin Chem 35: 179–180.
- 14. Paraoan L, Grierson I (2007) Focus on molecules: cystatin C. Exp Eye Res 84: 1019–1020.
- 15. Okamoto K, Mizuno Y, Fujita Y (2008) Bunina bodies in amyotrophic lateral sclerosis. Neuropathology 28: 109–115.
- 16. Tsuji-Akimoto S, Yabe I, Niino M, Kikuchi S, Sasaki H (2009) Cystatin C in cerebrospinal fluid as a biomarker of ALS. Neurosci Lett 452: 52–55.
- 17. Ryberg H, Bowser R (2008) Protein biomarkers for amyotrophic lateral sclerosis. Expert Rev Proteomics 5: 249–262.
- 18. Seronie-Vivien S, Delanaye P, Pieroni L, Mariat C, Froissart M, et al. (2008) Cystatin C: current position and future prospects. Clin Chem Lab Med 46: 1664–1686.
- 19. Madero M, Sarnak MJ (2009) Association of cystatin C with adverse outcomes. Curr Opin Nephrol Hypertens 18: 258–263.
- 20. Ryberg H, An J, Darko S, Lustgarten JL, Jaffa M, et al. (2010) Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics. Muscle Nerve 42: 104–111.
- 21. Nagai A, Ryu JK, Kobayash S, Kim SU (2002) Cystatin C induces neuronal cell death in vivo. Ann N Y Acad Sci 977: 315–321.
- 22. Nagai A, Ryu JK, Terashima M, Tanigawa Y, Wakabayashi K, et al. (2005) Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with cathepsin B. Brain Res 1066: 120–128.
- 23. Xu L, Sheng J, Tang Z, Wu X, Yu Y, et al. (2005) Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies. Neurobiol Dis 18: 152–165.
- 24. Nishiyama K, Konishi A, Nishio C, Araki-Yoshida K, Hatanaka H, et al. (2005) Expression of cystatin C prevents oxidative stress-induced death in PC12 cells. Brain Res Bull 67: 94–99.
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- 27. Magnus T, Beck M, Giess R, Puls I, Naumann M, et al. (2002) Disease progression in amyotrophic lateral sclerosis: predictors of survival. Muscle Nerve 25: 709–714.
- 28. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, et al. (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169: 13–21.
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- 30. Traynor BJ, Zhang H, Shefner JM, Schoenfeld D, Cudkowicz ME (2004) Functional outcome measures as clinical trial endpoints in ALS. Neurology 63: 1933–1935.


text: Refocus Tracks Your Goals for the Month on One PageJason Fitzpatrick7/18/09 2:00pmFiled to: GoalsTime managementTrackingPlanningPlanner3EditPromoteShare to KinjaToggle Conversation toolsGo to permalink Refocus is a simple printable template that allows you to lay out a handful of goals and track your adherence to those goals over the next 30 days. Tracking goals in a concrete and visual way is an excellent motivational tool. The Seinfeldian Chain, previously covered here, is certainly a strong example of the effectiveness and popularity of the technique when used as motivation for a single goal. The ReFocus worksheet allows you to track up to five goals over a month. From the author's web site: The end result looks like a cross between a Scantron form and Benjamin Franklin's Thirteen Virtues form. The purpose of this form is purely to give me a sense of accomplishment and to give feedback when I'm being unfocused. I still need to keep track of tasks that need to get done, but management of tasks and analysis of progress are now separated.Each circle is filled in completely, halfway, or not at all to indicate whether you made progress. If your goal was to eat healthy food and you ate a great breakfast and dinner but went out for lunch and ate fast food, you might, for example, fill in a half circle for that day. To the side there is space for notes.If you like the layout and want to check out another well-designed planning sheet, check out the previously reviewed Day Grid Balancer. Keeping Focus [WhiteHatBlackBox]Reply3 repliesLeave a reply

subset: commoncrawl


text: Rory McIlroy's Club Specs Matthew S Club Champion Certified Titleist Fitting Professional June 17, 2011 By Matthew S Anyone from Titleist know what the specs of McIlroys clubs are? Including length, flex, tipping, shafts on wedges etc...?? We can see basics under the Players Tab on the website but wondering about things like length and lie. Also seems like he put the old 906F2 back in the bag for his 4/5 wood. Thanks Quote Reply


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posted by Thom Holwerda on Thu 3rd Jan 2013 21:23 UTC, submitted by Adurbe
"Ubuntu, once the darling of desktop Linux and the overwhelmingly popular choice for newcomers, may soon lose that role to Mint." I switched to Mint KDE, and have no intention of going back. By the way, KDE4 is finally good (don't hit me, Aaron) - fast, fluid, stable, pretty, and thanks to its versatility, a joy to use after a few hours of tweaking. Just... Please, unify Plasma and the regular widget style. This is insanity.


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Celtic clinched their third successive Scottish Premiership title with seven games to spare courtesy of a 5-1 win at Partick Thistle on Wednesday.
You could almost hear the champagne corks being popped on the green side of Glasgow from the fourth minute at Firhill as Anthony Stokes headed home Emilio Izaguirre's cross.
Refusing the lie down without a fight, the home side responded impressively and caused problems for the remainder of the half.
Yet they had no answer just after the break when 17-year-old Liam Henderson grabbed his first professional goal, coolly converting after collecting a cross.
With the song 'championees' reverberating around the ground, Celtic began to really assert their dominance, Stefan Johansen rifling home a third.
Christie Elliot turned the tide a little with an 85th-minute goal, only for Neil Lennon's men to put an emphatic stamp on the game courtesy of late goals from Stokes and Kris Commons.
In the evening's other game, Dundee United put breathing room between themselves and Inverness Caledonian Thistle with a 2-1 win.
In a meeting of fourth versus fifth, United were put on their way when Ryan Gauld finished off a fine move.
A fortuitous second came after the break, goalkeeper Dean Brill's clearance hitting Ryan Dow and finding the net.
Liam Polworth's screamer offered Inverness hope, but United clung on to leave themselves five points ahead of their opponents and just four off the UEFA Europa League spots.
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Hughett, Owasso, carded 67-73--140, defeated John Church (70-70--140) in a playoff for the first place trophy.
In the Super Senior division, Jerry Greer posted rounds of 75-73--148 to edge Bob Fouke, 77-72--149, for the title.
View results for Oklahoma Senior Stroke Play Golf Championship
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Playstation 3
Xbox 360
Nintendo hands-on (p)Wiiview
Published on 26th October 2006 by Ryan Garside
1 - Nintendo Wii Hands On
2 - Is the Wii a novelty?
3 - The games wii played
56 Comments
56 Comments
The Nintendo Wii is arguably the most anticipated gaming console… well, ever. This is a rather odd fact considering that the Wii has so drastically bucked the trend of games console development. Instead of the traditional addition of more brute power to the gaming system, Nintendo have gone for a far more subtle approach, hoping to entice us in with promises of an enhanced gameplay experience that will be delivered through the magical power of the Wii remote.
So, the best/only way for anyone to really tell you what the Wii will be like is someone who has spent some time with the console. Fortunately, Nintendo gave me the opportunity earlier this week, to get to grips with the Wii in all its glory; the remote, the nunchuck and some of their launch titles. Read on to find out why exactly I think the Wii will still end up in third place once the dust has settled on the next-generation battle.
What's it like to play the Wii
We arrived in a bleach white room, complete with whites couches, white floors and of course the white Wii. The Nintendo rep handed me and a fellow journalist hack a Wii remote and invited us to the screen whispering "Play, play, play." It felt very much likesome kind of religious ritual as he positioned us in front of the widescreen television. The tennis game of Wii sports shone out at us like a shrine to which we should worship, the Nintendo rep eagerly watching us with wide eyes - and then the game began.
This is how models look playing the Nintendo Wii
There is no doubting the Wii is intuitive. You raise your arm like you were throwing a ball, imagining a little furry, yellow sphere floating into the air before bringing your hand down to smash it over the net. As if some kind of instinct has taken over, my left handed (the game had to be stopped to set this up) journalist opponent instantly swung his arm round to bat back my serve. I panicked; fortunately my little Mii character did not, charging across the screen positioning himself for a return. Worried I might embarrass the little fella by missing I swung my arm again, hitting a back-hand that Andy Murray would be proud of deep into my opponent's court. He stretched, let out a little yelp of exasperation, before the ball rushed past him leaving me fifteen-love up.
Do we look silly?
No instructions, no tutorial, just jump in and play. It was simple and effective and everyone, including the Nintendo-rep watching us, was chuckling at our efforts. Then we switched and started boxing – a similarly instinctive, though far more tiring game. In this, you had to punch backwards and forwards with both nunchuck and remote, swinging your hands right and left to dodge, moving up and down to duck. Despite each round lasting only a minute the whole process was hugely active, the Nintendo Wii will put paid to Jamie Oliver's plans to go on a crusade about 'Fat kids play games'. The Wii generation will be super fit, super toned athlectic Gods amongst men. Well, maybe not - but at least they won't be fat like this generation.
Within these two games I really began to appreciate the nature of the Wii's appeal. Nintendo want games to become a natural experience, make us jump, make us move and make us have fun. There's something fundamentally amusing about seeing a man of 32 swinging his arms backwards and forwards, hysterically laughing as he makes a cartoon character throw punches - it's the beginning of slapstick gaming. With the Wii, Nintendo want to tap into our physicality, make it fun and make the gaming experience enjoyable for everyone.
And this is how normal people look - not very pretty is it?
1 - Nintendo Wii Hands On
2 - Is the Wii a novelty?
3 - The games wii played
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By Patricia Daddona
PBN Staff Writer
NEWPORT – Salve Regina University has named Scott C. Zeman, a dean at St. Thomas University, as its next provost and vice president for academic affairs.
Zeman will start in his new post effective July 1.
A historian, Zeman is dean of the St. Thomas University Biscayne College for Liberal Arts and Social Sciences in Miami Gardens, Fla., where he teaches in the department of history, philosophy and global studies.
He succeeds Salve Regina provost Dean de la Motte, who served in the post for eight years and will join the faculty as a professor of French.
"I look forward to welcoming Dr. Zeman into the Salve family," said Salve Regina President Jane Gerety in a statement. "I believe his skill and experience will serve us well as we continue on the path to greater distinction as an academic institution in the Mercy tradition."
Before being appointed dean at Biscayne in 2011, Zeman had been associate vice president for academic affairs at New Mexico Institute of Mining and Technology. In 2012, he was named "Administrator of the Year."
At St. Thomas University, Zeman launched first-year learning communities, started a review of the general-education curriculum and helped establish the Center for Community Engagement. Other accomplishments include his work in expanding the Institute for World Languages and Cultures.
He also led an effort to create the university's Quality Enhancement Plan to improve student writing across the curriculum and developed partnerships with the fourth-largest PK-12 school district in the nation, the Miami Dade County Public School District.
Zeman is the author of two books, "Chronology of the American West" and "Atomic Culture: How We Learned to Stop Worrying and Love the Bomb," which he co-edited with Michael Amundson. He is working on a third, "Magazines and the Bomb: Inside American Popular Periodicals and the Atomic Age," which is to be published by University Press of Colorado.
Zeman earned a doctorate and bachelor's degree at Arizona State University, and a master's degree at the University of New Mexico.
"I am greatly honored to have been chosen to serve as Salve Regina's next provost," Zeman said. "Salve Regina is a wonderful institution with superb leadership under Sister Jane, a deep commitment to its mission, and a strong sense of community."
Tuesday, March 21
Thursday, March 23


text: Verbum Is a Simple, Theme-Friendly Word Processor for WindowsKevin Purdy3/01/11 6:05amFiled to: DownloadsWord ProcessorTextText editorWindowsOfficeFeatured Windows Download17EditPromoteShare to KinjaToggle Conversation toolsGo to permalink Windows only: Verbum doesn't have an Office-style "Ribbon," but it's not a code-friendly developer's tool, either. It's simply a word processor that supports most formats and seems really usable and friendly, even in its current alpha state. Advertisement All the basic text functions are in place in Verbum although Office or OpenOffice veterans may likely find something that's not available, or at least not in the same functionality. But Verbum doesn't aim to be anything more than a light word processor (running about 87 MB of memory on my system, but that's light, comparatively). And if you're into getting just the right look for all your apps, Verbum likely has a skin for you. You can customize the colors and buttons, but the defaults included fit most schemes, with variations on dark, blue, clear, and other standards. Advertisement Verbum is a free download, although still in alpha, for Windows systems.Verbum 2012 Alpha 1 [Rizone3 via CyberNetNews]Reply17 repliesLeave a reply


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COLUMBIA, S.C. (AP) — South Carolina Gov. Nikki Haley says a report on a massive security breach in the state's tax collection agency shows officials could have done more to protect personal information for nearly 4 million taxpayers.
She also said Tuesday that she also has accepted the resignation of Department of Revenue Director Jim Etter effective at the end of the year.
Haley says the report from computer security firm Mandiant found South Carolina made two mistakes. She says it didn't require two different ways to verify when someone was trying to get into the system to look at tax returns and it did not encrypt Social Security numbers.
The breach involved people who filed electronically. Haley says the hacker now has access to 3.3 million bank account numbers.


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Shuttle G6 Series. Nice new design with cool features
Shuttle G6 Series is a new Barebone design from Shuttle. If you ask us, it looks very good and it's a good update for the G5 models that started to appear back in 2004.
The deluxe model also got some nice feature such as fingerprint scanner, WLAN, Bluetooth, Dolby Digital Live!, and DTS Connect and of course a HDMI port.
Shuttle XPC Barebone SN68PTG6 Deluxe: powerful AMD AM2 small form factor (SFF) PC with HDMI port
More style, more performance and more features.
Shuttle Inc., SFF market leader and manufacturer of multi form factor solutions, today introduced a SFF PC Barebone with revolutionary functionality. The first of the new G6 line, the Shuttle XPC Barebone SN68PTG6 Deluxe features an integrated fingerprint scanner, WLAN, Bluetooth, Dolby Digital Live!, and DTS Connect.
Endowed with a NVIDIA GeForce 7050PV / nForce 630a chipset, Shuttle's new SFF PC supports both current AMD AM2 and future AM2 multiple core processors. Furthermore, this impressive black aluminium PC can also accommodate up to 4 GB of DDR2-800 RAM in dual channel mode.
"Following the successful introduction of the first Intel SFF PC Barebones with HDMI, now come models supporting 64 bit AMD processors," explains Tom Seiffert, Head of Marketing & PR at Shuttle Computer Handels GmbH. "The suffix Deluxe denotes new XPC Barebones that are especially well equipped."
A Windows Vista compatible NVIDIA GeForce 7050PV graphics processor delivers rapid onboard graphics, and there's an HDMI port (DVI via an adapter) and a VGA output for the utilisation of dual monitors. For even greater 3D performance, the Shuttle XPC Barebone SN68PTG6 Deluxe's PCI Express slot can be loaded with a high performance graphics card.
High connectivity is provided for in the form of WLAN, gigabit LAN, and a Bluetooth module. There's also the Speed-Link function allowing for direct connection to PCs by USB, and two eSATA ports for additional external drives.
Finally, a long life is guaranteed by the top-quality main board solid capacitors, and the energy needs of the whole system are taken care of by a reliable 300-Watt power supply and its generous reserves.
If you're willing to forego the Deluxe's great features, then Shuttle also offers the XPC Barebone SN68PTG5 with a 250-Watt power supply, and without WLAN, Bluetooth, Speed-Link, and fingerprint scanner.
Technical details:
* NVIDIA® GeForce 7050PV/nForce 630a chipset
* Supports AMD® Athlon[TM]64 X2, Athlon[TM]64 und Sempron[TM] series (HyperTransport 1.0) processors
* Up to 4 GB dual channel DDR2-800 RAM (OC to 1066 MHz)
* NVIDIA® GeForce 7050PV graphics with HDMI/HDCP
* 8-channel HD Audio with Dolby® Digital Live! and DTS® Connect
* 1x PCI-E X16, 1x PCI
* Gigabit LAN
* 2x FireWire, 6x USB 2.0
* 2x SATA2, 2x eSATA
* Bluetooth 2.0+EDR (Deluxe only)
* 802.11b/g wireless LAN (Deluxe only)
* USB Speed-Link technology (Deluxe only)
* Fingerprint scanner (Deluxe only)
* 250-Watt power supply / 300-Watt power supply (Deluxe only)
* 310(L) x 200(W) x 185(H) mm
Both Shuttle XPC Barebones will be available in the coming weeks. The recommended retail price is EUR 315 for the SN68PTG6 Deluxe, and EUR 239 for the SN68PTG5 (without VAT).
[via Pressrelease]


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The North Carolina Oyster Festival was this past weekend at Ocean Isle Beach. The Oyster Festival is the last big event that brings a crowd to our beach. The beach-going foot traffic will steadily decline from this point. The waterways have been quiet throughout the week, but the weekends have been super busy. The weather finally is making a turn to fall conditions with cool nights and north winds. The bull redfish run should continue for at least another week and then the speckled trout bite should be active.
The king mackerel fishing has been on fire this past week. Therefore, for those of you fishermen carving pumpkins, go ahead and slowly put down the knife and get the boat ready — the fish are biting. The kings have made their presence known by moving into the shallower waters of the Cape Fear shipping channel. In addition to being closer to the beach, this area is well known for producing big fish this time of year. Fishermen that fish the right time, tide and place can have one of their best king mackerel days of the year.
Clearly Hooked, captained by Austin T. Eubank of Carolina Beach, hooked a 39.65-pound king mackerel Saturday, Oct. 11, and won the Fall Brawl King Classic last weekend.
The crew won $19,306 for its first-place finish and its high finishes in other categories.
The Ocean Isle Fishing Center ran the tournament Saturday, Oct. 11, and Sunday, Oct 12. The tourney attracted 195 entries, and 130 boats fished Saturday.
Have you seen the weather forecast? We are expected to have the most stable weather we have had all year: light northerly winds at night switching to light southerly winds during the day. That should create a calm and predictable ocean, allowing all sizes of boats to target Spanish mackerel, king mackerel and bull redfish along our beach.
The fall fishing has finally fired off. King mackerel, Spanish mackerel, redfish and large schools of false albacore have resided off our coast, providing near shore anglers with some of the best fishing they have had all year.
By Capt. Derek Treffinger
Hed: Fall is here: Cooler weather brings hungry fish
Can you hear that?
Let us ease around the bend to investigate what is causing all that commotion.
Look at all those blue tails up and wagging at us. It was the kind of sight that makes even the most experienced redfish fishermen a little weak in the knees.


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Ubuntu 7.10 update woes
I do not know, but is it me? Does anyone else have problems when they just say "Yes" to the automatic updates on Ubuntu 7.10? The other day a new kernel came out that was related to Ubuntu 7.10. I woke up in the morning and saw the Red indicator of Ubuntu updates saying it was time to update my system. Still half a slepp I just clicked on it and proceeded with the update. |
Subject | Topic Starter | Replies | Views | Last Post |
Stupid blog | montezuma | 15 | 1,377 | Dec 29, 2007 8:37 PM |
You cannot post until you login.


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1994 Ford F-350 Billet Grills at Tuners Depot
Spyder® Front Billet Style Grill Grille (Chrome) - 92-96 Ford F-350 F350 |
Description: |
A nice sleek grill can make the difference for your Ford F-350 to a luxury / customized F-350. The difference can be compared to a supermodel before and after her nose job... technically a small part of the look, but these Ford F-350 Spyder Billet Style Chrome Front Grill will makes a huge difference to the overall look. The subtle change in the center of the subject changes the whole look of your Ford F-350. This Spyder Chrome Ford F-350 Front Billet Grill offers the look of more expensive grills in a more affordable design. Designed of a weather resistant material and molded for your F-350's exact grill area, the Spyder Chrome Billet Front Grill install fairly easy and can keep your Ford looking good for years to come.
Suggest Retail: | $199.99 | |
Our Price: | $134.95 | |
User Rating |
Shipping: | Free (Continental US) | |


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Dania Ramirez, 33, star of Lifetime's Devious Maids (premieres June 23 at 10 P.M.) empties out her purse for Us.
The star stays camera ready with the stash inside her Gucci tote. "I carry floss in case someone asks for a photo and there's stuff in my teeth," Ramirez (wed to director Bev Land, 35) says. "And red lipstick to get glamorous!" What else?
Victory Cap
"I have to have a hat in case my hair gets crazy. My husband's fits me, so I stole it. He's never getting it back!"
It's 5:00 Somewhere
"This may make me sound like a lush, but I keep a wine and beer combo opener. You never know when you'll have an impromptu picnic!"
Lacy and Racy
"I'm a total clean freak, and if I'm running around all day, I'll throw in an extra thong so I can change into a fresh pair. I keep it clean!"
Go-to Tome
"I just got done rereading The Secret. I go back to it every once in a while, especially after I've been working. It keeps me grounded."
Golden Girl
"My parents saved up for this gold name necklace. They moved to the U.S. from the Dominican Republic before me, but sent gifts when I passed a grade. It means so much to me!"
More Essentials
1. Diorskin Nude Tan, Paradise Duo Iridescent Blush and Bronzing Powder, $56, www.sephora.com
2. Donna Karen Cashmere Mist Pearl Essence Eau De Parfume Spray, $78, www.macys.com
3. Maybelline Great Lash Waterproof Mascara, $6.40, www.maybelline.com
4. Make Up Forever Professional Lipstick in Rouge Artist Intense, $20, www.sephora.com


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Pittsburgh, PA Thursday March 30, 2017 |
News Sports Lifestyle Classifieds About Us |
Can Pittsburgh learn to love bikes? Sunday, May 18, 2003 By Tatyana Margolin, Post-Gazette Staff Writer
Just after 5 p.m. on the last Friday of each month, cyclists gather by the dinosaur outside the Carnegie Library in Oakland. They linger, socializing as rush hour thickens. When it's just right -- bumper to bumper -- they launch, en masse, into the middle of it.
These are the people of Critical Mass, bike riders who band together to assert equal rights on the road -- and to promote the benefits of biking.
But while the group here is small, attracting 20 to 60 riders a month, many believe a critical mass of bicyclists -- activists or not -- is one ingredient that Pittsburgh needs to become the kind of hip place that attracts talented young workers now and in the future.
"A bicycle-friendly city is a more forward-thinking place, with more open people and a more natural lifestyle," said Christian Reed, 23, a graduate student at Carnegie Mellon University. Computer scientists, graphic designers, artists and other members of what Carnegie Mellon University professor Richard Florida calls "the creative class," love to bike, Reed said.
Bicycling Magazine in 1990 ranked Pittsburgh among the 10 worst biking cities in the country. Portland, Ore., a city known for its quality of life and as a place that draws young people, was ranked the best biking city.
Pittsburgh officials say the magazine's rating spurred a number of efforts that have erased any possibility of a repeat performance. And while avid cyclists don't view Pittsburgh as a biking paradise and see the actions taken so far as baby steps, neither do they think it's still among the country's worst.
Tough commute
Three mornings a week, C.J. Mikkelsen of Friendship loads her bike onto a bike rack and gets on the bus.
Mikkelsen became a bike commuter after the Port Authority put bike racks on buses. "I had never taken public transportation before, but in the last two years, I have," she said. "By the time I get home from work, I forget all about my problems of that day."
Though 3.2 million Americans bike to work at least once a week, in Pittsburgh, Mikkelsen is one of a very small group -- estimated by several groups as between 50 and 100.
"Compared with other cities, such as Eugene, Ore., and San Francisco, commuting by bicycle in Pittsburgh does not exist," said David Skillman, who has lived and cycled in both cities.
One major reason why so few commute by bike in Pittsburgh is that it's perceived to be "unreasonably dangerous," said Amy Ring who has also lived in Boston, Seattle and San Francisco. "Pittsburgh drivers are completely unaware of pedestrians and cyclists."
Pittsburgh police have registered only one critical injury for a cyclist this year. And in the past five years, the numbers have remained steady, with one to two critical injuries a year, though Allegheny County Coroner Dr. Cyril Wecht has recorded three cycling fatalities since 1998.
Aside from fear of injuries, a major impediment to more commuting in Pittsburgh is that there aren't enough biking facilities.
Mikkelsen commutes one way only because she lacks shower facilities at work where should could change from bike clothes into a business suit. Others write off commuting for lack of secure bike parking and shower facilities.
Those concerns will be eased somewhat when the Port Authority opens its Bike Station facility, expected by the end of the year. It will stand next to the First Avenue light-rail station near the Eliza Furnace Trail and will include secure bike lockers, bike rental, showers and bike maintenance services, as well as a snack bar.
Policies at some institutions also inhibit biking commuters.
"I quit riding to work because they wouldn't let me bring my bike inside," said Joanne Flynn, assistant professor at the University of Pittsburgh. While at Pitt, Amy Enrico stopped for the same reason -- her bike wasn't allowed inside the School of Public Health.
Kathleen Miller, who handles alternative transportation policies for Pitt, pointed out that the university provides outside racks and secure lockers for cyclists. But what about the avid cyclists who work far from the secure lockers and fear leaving their bicycles outside?
"Some people come here with really nice cars, and they might want to bring their cars into the office," said Miller. "I guess there is some amount of risk that's part of anybody's commute."
At Carnegie Mellon University, the picture is different. You can store your bike in your office. Just don't ride down the hall.
Three steps away
Compared with leading biking cities, Pittsburgh's policies are not adequately conducive to encouraging commuters, bike experts say. However, conditions have improved.
The city has built bike trails, the Port Authority has equipped some buses with bike racks and cycling advocates have surfaced.
"We are getting there," said Mayor Tom Murphy, himself an avid cyclist, adding that Pittsburgh is three steps away from becoming a great city for biking.
It must increase the miles of off-road trails, improve the system of marking and signing bike routes and create bike stations for cyclists to safely store bikes, he said.
Federal money, allocated under TEA-21 (Transportation Equity Act for the 21st century) could finance the improvements if it's released by the government. And the city would provide the labor.
Murphy pointed to the number of bike trails as proof of his dedication to cycling. Since taking office, he has worked on a new parking station and new signs that will direct cyclists from one trail to another.
Even the most jaded bike commuters praise the Eliza Furnace Trail, a 2.6-mile stretch connecting Greenfield with Downtown. Murphy opened it in 1998 at a cost of $200,000.
David Rollins, a Carnegie Mellon student, called it "the shining star of Pittsburgh for cyclists. I can get from CMU to Downtown without riding more than a mile on an actual road."
Eliza Furnace still lacks a connection to other trails, though. Downtown, it stops near the jail without signs for a nearby bicycle-friendly route, emblematic of a major issue facing Pittsburgh cyclists.
"When I first came here, I was gung-ho to ride in this city." said Christian Reed, a Vermont native. "They've got parks, I thought, so I'll be able to mountain-bike here. Turned out that the trails are far [apart] and disconnected."
"We are missing several connection points," agreed Andy Baechle, director of Friends of the Riverfront, a group that works on continued expansion of the bike trails.
"One [connection] is near Sandcastle on the south shore of the Monongahela. The Hot Metal Bridge [spanning the Monongahela between the South Side and Hazelwood] is another. We are also trying to do a temporary trail construction in front of Heinz Field."
Having a plan
Successful bicycling programs have political leadership, organized cycling constituents and a responsive administrative staff, including engineers and landscape architects, said Ben Gomberg, Chicago's cycling coordinator.
Great biking cities also have comprehensive Bike Plans, which outline goals and deadlines.
An organized cycling constituency is beginning to coalesce in Pittsburgh. It is small compared with those in other, better-known biking cities, but momentum is building.
Last year, after he was struck while biking by a car that did not stop, David Hoffman started Bike Pittsburgh, Western Pennsylvania's only cycling advocacy organization. The 75-member group wants to make the city safe, accessible and friendly to bicycle transportation.
"The cities that are really doing a terrific job at accommodating cyclists consider the bicycle almost every time a road project comes about," said Bike Pittsburgh board member Louis Fineberg. "This kind of mentality does not exist here."
Though many argue with its pace, cyclists agree that progress has been made under Murphy's leadership.
Recently, Murphy adopted a comprehensive Bike Plan. While the plan lists creation of a full-time bicycling coordinator as one of the top priorities, the mayor does not plan to appoint one. He believes that city worker Hannah Ehrlich dedicates a sufficient amount of her time to cycling issues.
Cycling advocates disagree, pointing out that most bike-friendly cities have full-time cycling coordinators. Chicago has five full-time bicycling staff members and a set of consultants and interns. Portland, Ore., has three full-time employees.
Pittsburgh currently has fewer than five miles of bike lanes, and Murphy said creation of new bike lanes was his top biking priority for the year. He said he would create a team to determine streets eligible for bike lanes.
Sustainable Pittsburgh's Urban Cycling Committee, a coalition of groups representing the region's bicycling community, has already identified a number of city streets as potential locations for bike lanes and listed them in a letter to Murphy.
Most are in the East End and would serve to connect Frick, Schenley and Highland parks.
A second set of bike lanes is targeted for the South Side, complementing the South Side segment of the Three Rivers Heritage Trail. The third set is in the West End, providing a link from the West End toward East Carnegie and the Montour Trail.
Bikers say Pittsburgh has the fundamental elements of a great cycling city: challenging terrain, beautiful country roads and streets with bike lane potential.
"I have biked through many neighborhoods in Pittsburgh, made many friends and visited many shops on a whim," said Devon Yates, 24, of Highland Park, a mechanical engineer. "I came to love Pittsburgh through cycling, and have chosen to stay here because of it, though I am often frustrated with the obstacles."
Her latest obstacle was last month , when she joined 75 other cyclists for the monthly Critical Mass ride outside the Carnegie Library in Oakland.
They began moving slowly down Fifth Avenue amidst thick Friday evening rush hour traffic. A police car joined the Critical Mass ride on Forbes Avenue, eventually stopping it at the intersection of Craig and Baum. There, Yates and three other riders were arrested.
The four spent a night and jail on several charges, including failure to disperse, disorderly conduct and obstruction of public passage.
Yates, who is contesting the charges, was particularly disturbed by the last one. "We were not blocking traffic," she said. "We are traffic."
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If we continue to walk on eggshells to avoid offending these hypersensitive young adults, we are empowering their victimhood status. If we continue to indulge their irrational demands, we are robbing them of the opportunity to learn how to function independently in the real world.
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I never set out to become a poster girl for helicopter parenting. In fact, I despise the term, and would much rather be called a protective parent. Somewhere along the line, though, cautious parents like me became misunderstood, even maligned, in the media.
Last weekend, my husband and I were totally flummoxed by a robin who crashed into our dining room window over and over again. We were desperate to hel...
I decided my mother was at fault each time I felt like I didn't grow up to be exactly the person I wanted to become.
What if the best way to help kids learn is to stop trying so hard to keep them safe? Hear popular TED speaker Gever Tulley's radical argument for letting kids play with power tools and other things that will make parents squirm.
My suggestion is to switch the focus from other moms, and what other moms are doing, to your own kids. Are your kids happy and healthy being co-sleeping french fry eaters? Awesome!
Everyone has an opinion on your parenting methods. The advice comes at us from medical professionals, friends, family and even strangers on the street. We are exposed more than ever before to more information, but also more evaluation and more judgment
The term "monster parent" was first coined in Japan to describe excessively protective parents who meddle in every aspect of their children's lives, and constantly complain to and about their teachers.
Helicopter parents usually have the best intentions -- to protect their children from life's hardships and prepare them for adulthood -- but as with many other aspects of parenting, the results don't always match the intentions.
In our fast-paced and competitive society, the stresses children face by over-ambitious parents often goes unnoticed. On behalf of the millennial generation, below are seven things helicopter parents everywhere need to understand.
The more we teach our kids that nature is dangerous, creativity is out of bounds and physicality is not to be tolerated, the more I worry for our society.
An enraged New York father allegedly showed up at his daughter's high school on Wednesday morning "swinging a heavy chain with a padlock and demanding...
When did lying to a child in order to foster confidence become more important than teaching him coping skills and how to accept weakness or manage failure? When did babying a child become more imperative than teaching her the lesson that not all kids are winners all the time and in every arena?
Perhaps my heart is two sizes too small, but even as a kid, I was not a fan of playing dress-up and knocking on doors asking for handouts. It was awkward and degrading.
Written for Slate by Dan Kois I didn't expect to be one of those parents who has opinions about playground equipment. Before we moved to the subu...
I often say that I have never actually met a helicopter parent. At least not one who describes themself that way. Everyone KNOWS a helicopter parent -- one who hovers and intrudes and smothers -- but they are always someone ELSE. I can't say that anymore.
Sometimes I purposely make the whirring noise of rapidly spinning propellers to punctuate the fact that like many Manhattan mothers I am called a "helicopter."
Fiction of all sorts, including nursery rhymes, allows us to try out conflict in a safe way. That's the point, it's where the thrill comes in; we're scared, then reassured the danger isn't real.
Letting go is the most difficult part of parenting. But it is also the most essential. Clinging to our children until we leave claw marks on their bodies is detrimental to their growth. And it doesn't make us any happier either.
Are parents as a whole more protective these days? And where is the line drawn between good protection (seat belts and not letting your kids drink bleach) and being overprotective to where it is stifling for them. I think about this sometimes.
Overprotective parents here's a message for you: If you want your kids to get more activity, you may want to back off. Those are the findings from ...
Welcome to Bubble Boy Nation, a place inhabited by overprotective parents, delicate, overindulged children, and two major political parties that routinely capitulate to legions of lobbyists.
Get top stories and blog posts emailed to me each day. Newsletters may offer personalized content or advertisements. Learn more.


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Description: Simplicity Appliques Disney Baby Iron On My Hunny- Applique with Pooh holding a sign with a caption of "My Hunny" and has bee accents. It is done in Tan, Brown, White, and Rust, and is approximately 4"x 5 1/8".
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Steal Alert: Kitchen Aid on Sale at Totsy!
Saying bye-bye to summer is sad, but awesome Labor Day sales make us happy!
-April Daniels Hussar
As sad as it is to say goodbye to summer (noooooo!!), there's a lot to be said for fall. Beautiful leaves, that "back-to-school" feeling… and comfort food cooking! I'm just about ready to start thinking about roasts, soups, stews and pies, so I was excited to see this sale on Kitchen Aid on Totsy.com (the flash sale site for moms and kids) — such high quality stuff!
This enamel and steel roaster above comes with a sturdy rack that will fit a 24 lb turkey or your favorite roast, not to mention lasagna and other baked dinner delights. YUM! ($59.99, regularly $69.99)
And this 7.5 quart, ovensafe. stockpot is 20% off. Simmering ahead! ($39.99, regularly $49.99)
Plus, there's free shipping site-wide on orders over $75. Sweet. This sale ends early Tuesday morning, so check it out at www.TOTSY.com over Labor Day weekend!


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Department and UIS Links
This is the body content for your website. Because Web page readers prefer to scan text, try to avoid long, dense paragraphs of text. Change your paragraphs of text into lists as often as you can.
This is a Sub-Head – Use Caps/Lower Case and Heading 2.
Getting Started at UIS
- About UIS
- Academic Programs
- Admissions
- Registration, Tuition, & Fees
- Financial Aid
- Future Students
- Housing
- International Students
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- Visit the Campus
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Important Websites for Students
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- Registration Deadlines & Semester Schedule
- Course Schedule
- Office of Disability Services
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- Student Life
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Carhartt Chain Link Knit
Retailers' Descriptions
Here's what other sites are saying:
Trust the Carhartt Men's Chain Link Knit Hat for all-day warmth and comfort. It's made of acrylic knit fabric with a polyester spandex fleece ear band and the chain-link knit pattern adds style.
- Altrec Outlet
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previously retailed for:
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The Carhartt Chain Link Knit is not available from the stores we monitor. It was last seen October 22, 2012 at Altrec Outlet.
If you're looking for a new winter hat, check out the best reviewed current models.


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Hohle Birne Clown Mask
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The Hohle Birne Clown is an impressive clown mask Foamlatex and is strongly reminiscent of our Helmut Kohl, who has probably seen the glass too deep again.The meticulous clown mask the stupid three peep forming fun maker is hand painted and very high quality.
The super soft face mask is made of breathable, skin-colored foam latex, has a pretty good fit and also transmits a portion of the facial expression of the wearer.In addition, the foam latex material is breathable than normal latex mask which you can not easily sweats.With the brilliant foam latex masks you turn yourself quickly in a completely different person, without being equally obvious that you are wearing a mask!
- Material: Foam Latex Latex


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MarketWatch: Increasing Health Care Costs Force Employers To Focus On Health Care Reforms
In her MarketWatch (5/6) blog, Kristen Gerencher writes that Len Nichols, a health economist at the New America Foundation, described in a conference call "a new study from the foundation" that examined "how high health-care costs are putting U.S. employers at a significant competitive disadvantage compared with the health-care burden shouldered by other industrialized nations. The problem will get worse unless financing for health coverage starts to shift away from the employer-based model, Nichols said." Gerencher adds that "groups of big employers ranging from AARP to Safeway to Wal-Mart with names like Divided We Fail, the Coalition to Advance Healthcare Reform and Better Health Care Together are calling for comprehensive change, a marked departure from employers' role in the last attempt at national health reform in 1993." To increase competiveness in the global market, "Nichols suggests eliminating or capping the tax exclusion that workers get for their employers' premium contributions and cashing them out by requiring employers to convert premium contributions into higher wages that workers could use to buy insurance on their own. For workers who can't afford it, he also recommends a sliding-scale tax credit."
BusinessWeek: Japanese Auto Makers Target Seniors
BusinessWeek reports that Japanese auto makers "are keen to keep seniors behind the wheel. Although few admit to targeting older customers with specific models, many new technologies or design trends are being developed with older drivers in mind." Toyota has "approached Ryuta Kawashima, a professor at Tohoku University, who chairs a 'mobility and smart aging' study group at the university, to help develop a car of the future. One idea is for the car to recognize how the driver normally drives, such as the way he or she accelerates or holds the steering wheel. If the approach to driving changes significantly, for instance, accelerating for no obvious reason, the car could automatically slow."
CNN/Money: Candidates Using 'Fuzzy Math' During Campaigns
CNN reports, "It's a good thing they're not running for accountant in chief. When it comes to selling their economic proposals as fiscally responsible, all three presidential candidates have managed to do some funny math." Democratic candidates "frequently cite their plans to let the Bush tax cuts of 2001 and 2003 expire for high-income taxpayers as a way to pay for their initiatives." That revenue "certainly could go a long way toward paying" for their health care reforms, but not the rest of their proposals. And "some of their other cost-saving measures, such as modernizing the health system and reducing wasteful health spending, are not easily quantifiable." McCain's campaign says his proposed tax cuts "will stimulate economic growth and maintain a healthy level of tax revenue. But studies – including one by Holtz-Eakin in his capacity as Congressional Budget Office director in 2005 – suggest that tax cuts don't pay for themselves over time."
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Mathew Barnett: Principal, Nicolas Junior High, Fullerton School District.
Editor's note: Commentary's Spark series includes Spark of Innovation, spotlighting local engineers and scientists, to encourage Orange County students to see career possibilities for themselves in science, technology, medicine and engineering, and Spark a Passion for Science, highlighting teachers, administrators, parents, students and organizations focused on improving STEM education in Orange County schools. Bill Blanning and Science@OC coordinate the Spark series.
What are you teaching in class right now? What is the real world application? I am the principal at Nicolas Junior High, which has seventh- and eighth-grade students. Our goal for our students is to have real-world learning experiences every day. We want students to understand that STEM is not just about one or two subjects, instead, it is about applying all of their skills and abilities toward engaging activities.
What do you see as the biggest single challenge in teaching science and math? Can you recommend a solution? Our biggest challenge with math and science education is that students believe that they are either good at these subjects or they are not. If they feel that they are good at science and math they try their best all of the time. If they feel they are not good at math and science they tend to give up when things get hard. Our challenge is to help students discover that they don't only have a certain fixed amount of math and science skill, rather, they can get better at subjects that they find challenging by trying hard. They need to know that putting forth a lot of effort will help them learn new and different things. We want them to learn to persevere in challenging situations.
What would be the most successful outcome of your work? What impact would it have? The most successful outcome of my work is to get students so engaged and captivated in subjects that they do not want to stop learning. If they find their learning tasks and activities interesting like that, they will be more connected to school and more motivated to do well in all areas of their lives.
Who or what "sparked your passion for science"? When did you make your career decision? When I was in high school, I took a wonderful physics class. I remember each of the projects that I did in that class. I remember that we had a golf ball launcher project in that class. I worked with my Dad and a family friend to design and build my launcher. From that moment on, I knew I could design and build things using science. I still think that's an awesome thing.
Where did you go to college? What degrees do you have? I have a bachelor's in Liberal Studies from Concordia University, Irvine, a master's of science degree from Pepperdine University and a Ph.D. from Claremont Graduate University.
Looking back at your years in school, which courses best prepared you for your work today? My work in graduate school prepared me most. In my masters program I learned about how to work with people with different viewpoints and in my Ph.D. program I learned how important connections between students and teachers are. Both of these things are really important to my job. I know that we need to connect to students' interests and let them know that they have people that believe in them and will help them be successful.
What makes you particularly well-suited for your job? I have a passion for the community where I work. I really want to make Nicolas Junior High a point of pride in my school's community. This keeps me centered on my work.
What part of your job gives you the most satisfaction? I really like seeing students doing interesting learning activities. When kids are really into learning about a subject and talking about the thing they are learning about really excitedly, it's magic. I love seeing that.
Are you involved in the Arts in any way? I go to all of our Arts performances and encourage students who are involved in visual and performing arts. I love to see our band, choir and dance classes perform. It's great to see students showing how proud they are about the skills they have developed and get up in front of audiences to show what they know.
What is the best advice you received that has helped further your career? To hire people smarter than you are. Smart people have newer, different and better ideas than you do and will make your school better.
What would you tell a student who may think a STEM career is beyond his or her reach? To work hard to achieve their goal because hard work pays off.
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n keeping with our philosophy of protecting the natural elements, our inn is designed to be environmentally low impact with a strong emphasis on renewable energy and ecological systems.
We believe that we have an obligation to protect the environment and reduce the impact of tourism by using eco-efficient energy and water systems, waste management practices and preserving the natural environment.
All of our energy is provided by solar panels and wind generation. Our lights and ceiling fans are energy efficient.
All the water from the showers and sinks supports constructed wetlands, providing controlled nutrition to a variety of plants. The toilets are low-flush, reducing water usage and the waste is filtered into composting units eliminating septic tanks. This is extremely important when building so close to the sea.
The planning design of Balamku considered the protection of the many local species of trees and plants. We are proud of our efforts to protect the endangered trees on the property which include a variety of palms, zapote (the original source of chewing gum), sea grapes (Uvas) and more. We are continuously planting hibiscus, bougainvillea, banana trees, papaya, melon, watermelon, salvia (aloe vera), cactus and other local species.
Each unit is situated to maximize the natural ventilation as well as the view of the sea.


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Home · Departments · Accounting · Research · McCombs Accounting Research Conference · 2012 Conference
This year's conference is hosted by Professor Volker Laux.
Sponsored by:
All events will be held at The University of Texas' AT&T Executive Education Conference Center located at 1900 University Avenue in Austin, Texas. Find driving directions here.
Please note: This conference is by invitation only.
We are happy to welcome our distinguished speakers and guests and look forward to engaging with you all.