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Patient-reported outcome (PROs) measures are being used more frequently in investigational studies of treatments for moderate to severe plaque psoriasis. The objective of this study was to examine the relationships among the Dermatology Life Quality Index (DLQI), the Short Form 36 (SF-36), and the EuroQOL 5D (EQ-5D) and to assess their validity, responsiveness, and estimates of minimum important differences.
A Phase II, randomized, double-blind, parallel group, placebo-controlled, multi-center clinical trial assessed the clinical efficacy and safety of two doses of subcutaneously administered adalimumab vs. placebo for 12 weeks in the treatment of 147 patients with moderate to severe plaque psoriasis. This study provided the opportunity to evaluate the validity and responsiveness to change in clinical status of PROs instruments. Patients completed the DLQI, SF-36, and EQ-5D questionnaires at baseline and at 12 weeks. Blinded investigators assessed the Psoriasis Area and Severity Index (PASI) scores and the Physician's Global Assessment (PGA) scores of enrolled patients. The responsiveness of the measures to changes in the clinical endpoints from baseline to Week 12 was assessed. Estimates of minimum important differences (MID) were derived. All analyses were performed with blinded data; findings and conclusions were not biased based on treatment condition.
The dermatology-specific DLQI was highly correlated to clinical endpoints at baseline and at Week 12, and was the most responsive PRO to changes in endpoints. Compared with the SF-36, the EQ-5D index score and VAS scores were generally more highly correlated with clinical endpoints, but displayed about the same degree of responsiveness. The most responsive SF-36 scales were the Bodily Pain and Social Functioning scales. Estimates of the MID for the DLQI ranged from 2.3–5.7 and for the SF-36 Physical Component Summary (PCS) score ranged from 2.5–3.9.
This study provides support for the continued use of the DLQI and SF-36 PCS in the assessment of treatments for psoriasis. On the basis of the results from this trial, the EQ-5D should be considered as a general PRO measure in future clinical trials of patients with moderate to severe plaque psoriasis.
Moderate to severe plaque psoriasis has been demonstrated to have substantial impact on function limitations and psychosocial factors of patients with the disease [1–5]. Moreover, successful treatment of moderate to severe psoriasis – as assessed by improved physical functioning and reduction of signs and symptoms – has been shown to have a positive impact on social and psychological aspects of psoriasis [6–11].
Given the functional and psychosocial impact of the disease, studies of moderate to severe psoriasis patients often include both physician-assessed clinical endpoints and dermatology-specific patient-reported outcomes (PROs) to obtain a holistic view of the disease and treatment effects in patients . Such practices are bolstered by the assertion of the Medical Advisory Board of the National Psoriasis Foundation (NPF) that, even more so than physical signs, such as the percentage of body surface area (BSA) affected by psoriasis, the severity of psoriasis is "first and foremost a quality-of-life (QOL) issue" . The same values for percentage BSA involvement can result in very different degrees of impact for different patients, depending on the location of psoriatic plaques, the pain associated with the lesions and plaques, the extent of bleeding associated with the psoriatic lesions, and resulting functional limitations. The NPF Advisory Board suggests an alternative basis for defining mild, moderate, or severe psoriasis, predicated on QOL impacts of the disease. Similarly, the guidelines recently promulgated by the British Association of Dermatologists  for the use of biologics in psoriasis indicate that eligible patients must have a Psoriasis Area and Severity Index (PASI) score of at least 10 and a score on the Dermatology Life Quality Index (DLQI)  – a dermatology-specific validated PRO measure – of greater than 10.
A Phase II clinical trial of two dosages of adalimumab and placebo in the treatment of moderate to severe psoriasis provided an opportunity to further explore the psychometric characteristics – including responsiveness and minimum important differences – of the three PROs used in the trial: the DLQI; the general health-related QOL measure MOS Short Form 36 (SF-36) Health Survey ; and the general health status measure EuroQOL 5D (EQ-5D) [17, 18]. Establishing the reliability, validity, and responsiveness of PRO measures is necessary for their use in support of labeling claims, according to an FDA draft guide to industry . Reliability refers to the accuracy of a measure, while validity refers to the extent the measure actually is measuring what it purports to measure. Responsiveness is a component of validity and represents the PRO's capability to detect changes related to changes in the clinical status of patients or other relevant outcomes measures. Minimum important difference (MID) is related to responsiveness and provides guidance to those reviewing clinical trial results as to whether the statistically significant group differences or changes are clinically meaningful and important. Jaeschke and colleagues  define a minimal clinically important difference (MCID) (we use MID instead of MCID to avoid confusion) as "the smallest difference in score ... which patients perceive as beneficial and which would mandate, in the absence of troublesome side-effects and excessive cost, a change in the patient's management." Estimation of the MID – using several different approaches – is also emphasized in the FDA guidance and is consistent with recently published recommendations of health outcomes researchers [21, 22].
The objectives of the Phase II, randomized, double-blind, parallel group, placebo-controlled, multi-center clinical trial were to assess the clinical efficacy and safety of subcutaneously administered adalimumab vs. placebo using two dosage regimens for 12 weeks in the treatment of 147 patients with moderate to severe plaque psoriasis. The study included a screening period, a blinded 12-week treatment period, and a 30-day follow-up visit for patients not completing 12 weeks of active treatment or not entering an extension study. Time between screening and baseline visits was not to exceed 28 days. The trial achieved the objectives of the study in terms of safety and clinical efficacy endpoints .
Patients with a diagnosis of moderate to severe plaque psoriasis and an affected BSA of ≥ 5% for at least 1 year were eligible for the study. In addition to other inclusion criteria (e.g., age ≥ 18 years, willingness to give informed consent), patients had to be able to self-inject medication or have a designee or nurse who could inject the randomized assignment. Patients signed informed consent forms, and the study complied with FDA Good Clinical Practices, Health Protection Branch guidelines, and all other applicable ethical, legal, and regulatory requirements .
Frequently used as an endpoint in psoriasis clinical trials , the PASI  was the primary efficacy outcome in this trial. PASI is a composite index indicating the severity of the three main signs of psoriatic plaques (i.e., erythema, scaling, and thickness) and is weighted by the amount of coverage of these plaques in the four main body areas (head, trunk, upper extremities, and lower extremities). PASI scores range from 0–72, with higher scores indicating greater disease severity. PASI was assessed at screening and baseline, at Weeks 1, 2, 4, 8, and 12/Early Termination, and at the final follow-up visit.
Clear: no signs of psoriasis (post-inflammatory hypopigmentation or hyperpigmentation could be present).
The PGA scale is scored from 1 (Clear) to 7 (Severe). The PGA was assessed by the investigator at screening, baseline, and Weeks 1, 2, 4, 8, 12/Early Termination, and the follow-up visit. Each study site was to make every attempt to have the same investigator perform these assessments throughout the study for each patient.
Three PROs measures were used in the study and are the subject of the analyses reported here. All PROs measures were assessed at baseline and at Week 12 (or early termination, if applicable).
The DLQI was developed as a simple, compact, and practical questionnaire for use in dermatology clinical settings to assess limitations related to the impact of skin disease . The instrument contains 10 items dealing with skin (e.g., Item 1: "Over the last week, how itchy sore, painful, or stinging has your skin been?"). The DLQI score ranges from 0–30, with "30" corresponding to the worst quality of life, and "0" corresponding to the best score. The DLQI has well-established properties of reliability and validity in the dermatology setting [15, 26–28].
The SF-36 is a 36-item general health status instrument often used in clinical trials and health services research . It consists of eight domains: Physical Function, Role Limitations-Physical, Vitality, General Health Perceptions, Bodily Pain, Social Function, Role Limitations – Emotional, and Mental Health. Two overall summary scores can be obtained – a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score . The PCS and MCS scores range from 0–100, with higher scores indicating better health. The SF-36 has been used in a wide variety of studies involving psoriasis, including descriptive studies  and clinical research studies [6, 7], and has demonstrated good reliability and validity. Internal consistency for most SF-36 domains is greater than 0.70. The SF-36 has been shown to discriminate between known groups in a variety of diseases, is reproducible, and is responsive to longitudinal clinical changes.
The EQ-5D [17, 18] is a six-item, preference-based instrument designed to measure general health status. The EQ-5D has two sections: The first consists of five items to assess degree of physical functioning (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Items are rated on a three-point scale ranging from "No Problem" to "Extreme Problem" or "Unable to Do." Each pattern of scores for the five items is linked to an index score that has a value ranging from 0–1, indicating the health utility of that person's health status. The specific linkage can differ from country to country, reflecting differences in cultures to the item responses. The second section is the sixth item on the EQ-5D, which is a visual analog scale with endpoints of "100" or "Best Imaginable Health," and "0" or "Worst Imaginable Health." It offers a simple method for the respondents to indicate how good or bad their health statuses are "today." The score is taken directly from the patients' responses.
Validity of the PRO measures was assessed in several ways. First, an assessment was made of the concurrent validity of scales and subscales (i.e., the extent to which PRO measures are correlated with one another). As a disease-specific PRO measure, the DLQI was expected to correlate moderately to extremely well with general PRO measures. Another important aspect of validity in this study was to assess the extent to which the PRO measures correlated with the clinical endpoints – PASI and PGA – both at baseline and at Week 12.
Responsiveness of PRO measures was assessed via two approaches. First, changes in these measures from baseline to Week 12 were correlated with changes in the PASI or PGA over the 12-week course of treatment within the trial. Concurrent improvement in both clinical measures and PRO measures was expected to result in positive correlations. The second approach to assessing responsiveness involved categorizing patients into responder groups based on the changes in their PASI scores from baseline to Week 12. This was done in two ways. First, a responder was defined as a patient with >75% improvement in PASI (consistent with the definition of success with the primary efficacy variable), and a non-responder was defined as a patient with a PASI improvement <50% (consistent with the definition of failure for a secondary efficacy variable). Tests of mean differences in improvement on the PRO measures were completed between the two groups. Secondly, in support of the estimation of the MID, discussed below, patients were further categorized by degree of PASI response, and assessed differences among these four groups: PASI improvement <25%; PASI improvement 25–49%; PASI improvement 50–74%; and PASI improvement ≥ 75%. Analyses of variance tests were performed among these four groups for changes in PRO measures.
In accordance with the FDA draft guidance  and consistent with recent recommendations from PRO researchers [21, 22], five methods were used to estimate MIDs of the PROs. The PRO change score corresponding to PASI 25-PASI 49 was the first estimate of MID, called MID-1. This was based on the assumption that patients would perceive a PASI improvement of 25% as beneficial. The trial did not provide data to test this assumption (e.g., there was no rating by patients of their overall improvements). A second estimate, MID-2, was based on the PRO change score corresponding to a PASI improvement between 50–74%. The PASI 50 is seen as clinically relevant, and, as such, this degree of improvement served as a secondary efficacy endpoint in this trial. A third method for estimating MID relied on the association of changes in the PRO measure with changes in the PGA. A non-responder was defined as a patient with a PGA change score of either "0" (no change) or "1" (slight increase in severity of disease) from baseline to Week 12. A minimal responder was defined as a patient whose PGA improved by either 1 or 2 points from baseline to Week 12. The third estimate of MID, MID-3, was the difference in the PRO score between non-responders and minimal responders.
In addition, two distributional methods were used to support the anchor-based MID estimates for the PROs [21, 22]. Based on evidence by Wyrwich and associates [31, 32], the standard error of measurement (SEM) can be used to approximate the MID. The SEM, which describes the error associated with the measure, was estimated by the standard deviation of the measure multiplied by the square root of 1 minus its reliability coefficient. Finally, there has been discussion  concerning a number of studies demonstrating that one-half of the standard deviation of a measure represents the upper limit of the MID . In estimating the SEM for the SF-36 and the EQ-5D, reliability estimates from the literature were used. The SEM for the DLQI incorporated the reliability estimated from the trial data, which was consistent with what has been found in the literature for this instrument .
Finally, it is important to note that all analyses were performed with blinded data (i.e., the statuses of patients with respect to their assigned treatment groups were not known).
A total of 147 patients enrolled and received at least one dose of study medication at 18 sites in the United States and Canada. Blinded data were available for the PROs for 147 patients at baseline and 140 patients at Week 12. Since the focus of these analyses were on the psychometric properties of the PROs rather than with efficacy, observed cases were employed rather than last observation carried forward or other methods for treating missing observations at the end of trial. The mean age of the patients enrolled in the trial was 44.2 years, two-thirds were male, and the preponderance were white (Table 1).
The results for the PASI and the PGA at baseline and Week 12, as well as the change from baseline to Week 12, are displayed in Table 2. The mean PASI at baseline was 15.7, which decreased by 8.9 points (improvement) to 6.8 by Week 12. The mean PGA at baseline was 5.5 (i.e., midway between "Moderate" and "Moderate to Severe"), and decreased (improved) by 2.1 points to 3.4 by Week 12 (i.e., between "Mild" and "Mild to Moderate"). In evaluating the improvement in the two clinical endpoints, it is important to keep in mind that these analyses included pooled placebo and active treatment groups.
1 Scored such that 1 = "Clear" to 7 = "Severe."
2Change scores are computed only for the 140 patients with scores at baseline and Week 12; sample size at baseline = 147.
The results for the DLQI, SF-36, and EQ-5D at baseline and Week 12, and the change from baseline are shown in Table 3. Based on blinded data, mean PRO measures improved during the course of the trial (a decrease in DLQI scores indicates an improvement; an increase in the SF-36 and EQ-5D indicates improvement). The greatest improvement in a DLQI item occurred for the first item, assessing how "itchy, sore, painful, or stinging" the person's skin felt (data not shown). Similarly, as shown in Table 3, the greatest improvement among the SF-36 scales was for Bodily Pain. The largest improvement among the five EQ-5D dimensions occurred for the Pain/Discomfort dimension (data not shown). Given these findings, it appears that improvement in pain and discomfort is the most pronounced among all PRO measures assessed.
1Change scores are computed only for patients with scores at baseline and Week 12; this number varied between 138 and 140, depending on the specific measure, as compared with the 147 patients at baseline.
The reliability of the DLQI, as assessed by coefficient alpha, was 0.89 at baseline and 0.92 at Week 12, indicating that this is a highly reliable measure, and in line with previous findings [27, 28].
Table 4 displays the correlations among PRO measures at baseline and at Week 12, as well as the correlations among changes in these measures from baseline to Week 12. There were a few trends evident form this data. First, all measures were statistically significantly inter-correlated. Second, with respect to the relationship between the DLQI and the SF-36, the DLQI correlated the greatest with the Bodily Pain and Social Functioning domains, both at baseline and at Week 12, and, for changes in these scores over the course of the trial. Third, the DLQI correlated highly with the EQ-5D index score, and these correlations were consistently higher than the correlations with the EQ-5D visual analog scale (VAS) scores. Fourth, the EQ-5D index score tended to correlate greatest with the Bodily Pain domain of the SF-36. Finally, the scores tended to be more highly correlated at the end of the trial than at baseline, consistent with previous findings .
1All correlations were significant at p < 0.001, unless otherwise noted. *p ≤ 0.05, **p ≤ 0.01, ns = non-significant.
Table 5 displays correlations of PRO measures with the two clinical assessments – PASI score and PGA – at baseline (first two columns of data) and at Week 12 (second two columns). In addition to almost uniformly greater correlations at Week 12 vs. at baseline – consistent with previous findings  – one can also note that both the DLQI and EQ-5D index score tended to be more highly correlated with the two clinical endpoints than any of the SF-36 domains. The SF-36 scales with the strongest association with clinical endpoints are Social Functioning and Bodily Pain.
1All correlations were significant at p < 0.001, unless otherwise noted. *p ≤ 0.05, ** p < 0.01, ns = non-significant.
An important attribute for a PRO measure is responsiveness to change in the clinical status of a patient (i.e., as a patient's disease improves, the PRO measures also improve). The last two columns of Table 5 display the correlations between changes in PRO measures used in the trial and changes in PASI scores and the PGA from baseline to Week 12. These data demonstrate that the DLQI is the most responsive of the PRO measures. The correlations between changes over the course of the trial in the DLQI total score and changes in the PASI score (r = 0.69, p < 0.001) and PGA (r = 0.71, p < 0.001) approach the correlation between changes in the two clinical measures themselves (r = 0.75, p < 0.001). In addition, the DLQI is the only one of the PRO measures to demonstrate equal responsiveness to PGA and PASI scores. The correlation between changes in the EQ-5D index score and the two clinical assessments was r = -0.57 (p < 0.001) for changes in the PASI to r = -0.44 for changes in the PGA (p < 0.001). Similarly, the correlations between changes in all but one of the SF-36 scores and changes in the PGA were smaller than correlations between changes in the SF-36 and the PASI.
A second way to assess responsiveness was to contrast patients who were defined as clinical responders with those characterized as non-responders. Given that the primary endpoint in the trial was defined as the percentage of patients achieving a PASI 75 response (i.e., ≥ 75% improvement in PASI from. baseline) by Week 12, a responder was defined as a patient with a PASI75 response. A non-responder was a patient with <PASI 50, since some of the secondary endpoints in the trial used this cut-off. The results of these analyses are displayed in Table 6. DLQI total scores for responders improved by 12.17 points, while scores of non-responders improved by 1.77 points. This difference was statistically significant (t = 9.0; p < 0.0001). All the PRO measures except for the SF-36 Physical Functioning domain were responsive, as defined by a statistically significant difference between responders and non-responders. The DLQI was the most responsive of the PRO measures, as evidenced by the size of the t-statistic and the effect size. The responsiveness of the EQ-5D index and VAS scores were generally the same as several of the SF-36 domain scores.
1Responder is defined as PASI improvement ≥ 75%; non-responder is defined as PASI improvement <50%.
While the estimates of responsiveness displayed in the last two columns of Table 5 take into account the full range of PASI change scores and their relationship to PRO change scores, the responsiveness analysis in Table 6 places patients in two categories – responders and non-responders. Table 7 defines four categories of responders: responders, defined as those with PASI improvements ≥ 75%; "partial responders," those with PASI improvement 50–74%, inclusively; "near responders," those with PASI improvement 25–49%, inclusively; and non-responders, with <PASI25. One-way analyses of variance were performed among these groups for each of the PRO measures. As can be seen by the size of the f-statistics, the DLQI was the most responsive of the PRO measures. In fact, only the DLQI was able to demonstrate statistically significant differences between responders and partial responders based on post-hoc significance tests among the four responder groups. These results for the DLQI total score with respect to differences among responder groups were similar to those reported previously in the literature, except that the improvement in DLQI total scores displayed in Table 7 was larger for each of the responder groups than for the equivalent responder groups described by Shikiar and colleagues in a study of efalizumab . As was the case for the data displayed in Table 6, the responsiveness of the EQ-5D index and VAS scores were generally the same as for most of the SF-36 scores. Finally, both the SF-36 MCS and PCS scores were responsive, but the MCS was substantially more responsive, indicating that the impact of the disease was both physical and mental, with the latter perhaps being more prominent for this study population.
1Pairwise comparisons between means were performed using Scheffe's test adjusting for multiple comparisons. 1 = improvement <25% vs. improvement 25–49%, 2 = improvement <25% vs. improvement 50–74%, 3 = improvement <25% vs. improvement ≥ 75%, 4 = improvement 25–49% vs. improvement 50–74%, 5 = improve 25–49% vs. improvement ≥ 75%, and 6 = improvement 50–74% vs. improvement ≥ 75%. *p < 0.05, **p < 0.01, ***p < 0.001.
2Negative change scores indicate improvement.
There is no one best way to estimate the MID for a PRO measure [21, 34]. Table 8 contains three different anchor-based methods for estimating the MID based on data from this study. MID-1 contains the estimate obtained from the scores from the "near-responders," shown as the PASI 25-PASI 49 group in Table 7; MID-2 contains the estimate corresponding to "partial responders" in the same table 7. MID-3 corresponds to the difference between non-responders for the PGA (defined as patients who had no change in score or a decrease in score by one point on this 7-point scale) and minimal responders for this same measure (defined as patients who improved by 1 or 2 points). The distribution-based estimates, the SEM and one-half the standard deviation of baseline scores are also reported in Table 8.
Note: MID-1 corresponds to the score for the PASI 25–49 group; MID-2 corresponds to the score for the PASI50-74; for MID-3 and MID-4, reliability estimates for computing SEM were obtained from the data in this study for the DLQI and from estimates found in the literature for the SF-36 and EQ-5D.
1MID estimates are not provided for the SF-36 Physical Function domain since there were not significant differences among responder groups.
Estimates for the DLQI MID ranged from 4.05 (for MID-1) to 6.95 (for MID-2), while the SEM was 2.33 and one-half standard deviation was 3.59. The MID results for the SF-36 PCS ranged from 0.51 (for MID-3) to 3.91 (for MID-1), with the SEM estimated as 2.71 and one-half standard deviation estimates as 5.12. For the MCS, the MID estimates included a decrease of 1.82 points based on a PASI improvement of 25–49%, but the other two MIDs were 6.05 and 6.61, respectively. The SEM for the MCS was 3.89 and one-half standard deviation was 5.61. Consistent with the MCS findings, decreases were observed for the Role-Emotional and Social Functioning domains for the MID-1 definition. The differences between non-responders and minimal responders ranged from 4.90 for Mental Health to 24.71 for Social Functioning (Table 8). The results for the EQ-5D index score demonstrated an MID ranging from 0.09 (for MID-3) to 0.20 (for MID-2). For the EQ-5D VAS, the available estimates ranged from 3.82 (MID-1) to 8.43 (MID-3).
A Phase II randomized clinical trial of adalimumab in moderate to severe plaque psoriasis provided the opportunity to evaluate the validity and responsiveness to clinical change of three PRO assessment instruments – one dermatology-specific instrument and two general health status instruments – all used as endpoints in the study. All analyses were performed on a blinded basis, since the main focus of these secondary analyses was on the psychometric qualities of the PRO instruments.
Although developed for a general population with dermatologic diseases, the DLQI has most frequently been applied to patients with plaque psoriasis . More recently, the DLQI has been used as an endpoint in clinical trials involving the newer class of biologics for treatment of moderate to severe psoriasis, including alefacept [6, 7], etanercept [9, 10], and efalizumab [8, 11]. The present study further establishes the reliability and validity of the DLQI and its responsiveness to change in the clinical status of patients over the course of a 12-week clinical trial, confirming previous findings . Changes in the DLQI total score demonstrated significant and sizeable correlations with independently obtained physician-assessed changes in the clinical statuses of patients. This indicates that the alleviation of psoriatic signs, as determined by clinical assessments, results in significant and marked improvement in dermatologic-related functional limitations and quality of life in patients with moderate to severe plaque psoriasis. Based on this study, the DLQI is a psychometrically sound and responsive measure of psoriasis-specific outcomes that captures more comprehensively the impact of clinical signs and symptoms on patient well-being.
Data were also used to derive estimates of the MID of the DLQI. Although the MID is defined as the smallest difference that a patient would perceive as beneficial, there were no patient-based assessments of change in this study. Hence, lacking a patient-based anchor, the data do not provide the basis for determining the smallest score that a patient would perceive as beneficial. We used both the PASI and the PGA, as well as two distributional approaches to derive estimates of the MID of the DLQI. These estimates ranged from 2.33–6.95. However, we believe that the PASI 50 is too conservative for estimating the minimum change that patients will find beneficial. Therefore, we believe the estimate based on PASI improvement of 25–49% or between non-responders and minimal responders provide better estimates of MID. Therefore, the results indicate that the MID is in the range of approximately 2.3–5.7, which is slightly higher than the range of estimates derived from Shikiar et al.  in an analysis of two clinical trials involving another psoriasis therapy. The distributional approaches resulted in the lowest estimates of MID for the DLQI, but it should be noted that the distributional approach to estimating the MID is considered supportive of the anchor-based methods [22, 35]. For example, the one-half standard deviation estimate is certainly clinically meaningful, but is likely not a minimum magnitude of change. Finally, the range of estimates incorporates another previous estimate of the MID of the DLQI of 5.0 .
Two general PRO measures were used in this study. In general, the EQ-5D index and VAS scores demonstrated higher correlations than the SF-36 scale scores with the clinical endpoints (Table 5). However, the responsiveness of these two EQ-5D scores was generally the same as the responsiveness of most of the SF-36 scores. Nonetheless, this study demonstrated that the EQ-5D performs at least as well as the SF-36 as a non-dermatologic specific PRO measure for this sample of moderate to severe psoriatic patients.
Although most of the SF-36 scores showed improvements associated with clinical outcomes, the MCS, Social Functioning, and Role-Emotional domain scores demonstrated decreases in the PASI 25–49% group. These findings may have been driven by several outliers and the relatively small sample size for this group. Alternatively, given that Bodily Pain and other physical domains may be more related to the signs and symptoms of psoriasis than Role-Limitations and Social Functioning, small improvements in PASI scores may not be directly associated with changes in these PRO domains. That is, larger changes in clinical outcomes may be needed to significantly impact the areas of physical function and well-being. This idea seems to be supported by the observed changes in the PASI 50–74% and other analyses. However, the SF-36 domain and summary scores demonstrated consistently reasonable validity and were correlated with clinical endpoints and DLQI scores.
The SF-36 PCS and MCS scores demonstrated good evidence of validity and responsiveness in this sample of patients with moderate to severe plaque psoriasis. There were demonstrable associations between changes in PASI score categories and changes in PCS scores, with the largest improvements seen in the PASI75 responder groups. The MID estimates for the PCS were in the range of 0.51–3.91, with the best estimate at approximately 2.5 points. The SEM estimate (2.71) also supports this range of MID values for the PCS. These results are consistent with previous research on the PCS scores in rheumatoid arthritis and other chronic diseases [29, 37]. The MID findings for the MCS were somewhat weaker, but there is evidence that a change of 4–6 points is certainly clinically meaningful. The MID for the EQ-5D index score was in the range of 0.09–0.22.
Given the impact of psoriasis on the functional ability of patients the importance attached to assessing physical function in psoriasis patients, the results of the present study provide positive support for the use of a dermatology-specific health-related PRO measure, the DLQI, in the assessment of psoriasis and responses to treatment. In addition, the correlation of SF-36 and DLQI indicates that disease-related changes in the SF-36 are largely dependent on two specific domains, Bodily Pain and Social Functioning. It appears that the DLQI total score, as a single index score, adequately captures the functional and psychosocial impact of moderate to severe plaque psoriasis. Further, the DLQI does so in a way that is substantially more responsive than the general health-related quality of life measures used to assess changes in patients' underlying clinical statuses. The importance of the DLQI in measuring psoriasis patients' disease statuses, both at baseline and after treatment, is underlined by recent UK guidelines that recommend the DLQI serve both as an indicator of biologic therapy need and adequate treatment response .
There were several limitations to the present analysis. The first relates to sample size and selection. The sample was limited to those meeting the inclusion/exclusion criteria if this Phase II clinical trial. Since this was a Phase II study, the sample size was smaller (N = 147) than typical Phase III studies involving moderate to severe psoriasis, thereby requiring even one to use even greater caution in extrapolating the results of this analysis. Other applications of the PRO instruments (e.g., other clinical settings or settings including non-biologic treatments) might not involve the same exclusions. Therefore, generalizability of these results may not be applicable to all clinical settings. Second, the DLQI is not the only dermatology-specific instrument to assess the impact of psoriasis on physical function and psychosocial factors. Other instruments have been developed [38, 39], but have not been used as frequently as the DLQI in psoriasis trials. Nonetheless, results reported here do not indicate whether the DLQI has relative advantages or disadvantages to these instruments. Finally, given that the MID denotes the minimum change that a patient would find beneficial, anchoring the estimates of MID to patient assessments of severity or change would prove useful, and the current Phase II trial did not include such assessments.
The findings of this study highlight the importance of capturing PRO measures in clinical trials of moderate to severe plaque psoriasis. This analysis provides additional evidence supporting the psychometric qualities and responsiveness of the DLQI as a disease-specific measure of PROs in psoriasis. The DLQI MID was determined as ranging from 2.3–5.7 points. While the DLQI provides the most reliable measure of clinical change, the data from this study demonstrate that the SF-36 and EQ-5D performed well as general measures of health status outcomes. While the SF-36 has been used in previous studies comparing psoriasis treatments [6, 7, 30], to date, there have been few applications of the EQ-5D in clinical trials of patients with moderate to severe plaque psoriasis. The results of this study indicate that these two instruments should be considered as a general health outcome measure in future clinical trials.
The work reported here was performed under a contract to the United BioSource Corporation from Abbott Laboratories. Lisa E. Melilli, DrPH, formerly of Abbott Laboratories contributed substantial important scientific and analytical suggestions and insights, and reviews of the manuscript. Mary Cifaldi, PhD, RPh., MSHA, of Abbott Laboratories provided invaluable reviews and comments on previous drafts of this manuscript. The authors thank Michael Nissen, ELS, of Abbott Laboratories for his editing assistance in the development of this manuscript.
Portions of these results were presented at poster and podium sessions at the European Meeting of the International Society for Pharmacoeconomic Research in Florence, Italy, November 2005.
The work reported here was performed under contract by the United BioSource Corporation to Abbott Laboratories. Authors 1, 4, and 5 are employees of the United BioSource Corporation, which performed this work under contract. Authors 2 and 3 are current employees of Abbott Laboratories.
RS was responsible for the planning and analysis of the research reported here. MKW provided key analysis and interpretation of the data, and revised the manuscript critically for important intellectual content. MMO contributed important clinical insights into the research. CST contributed suggestions for analysis and provided analytical support for the research. DAR contributed to the analysis and interpretation of the research and reviews of the manuscript. All authors reviewed and approved this manuscript prior to submission.


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The FRench Network Operators Group (FRnOG) gathers around people in the areas of DNS security, internet research and services in France.
The FRnOG's mission is to contribute to enhance the quality of service for the internet in France by providing a place to exchange information and communication between internet companies or associations in France.
The 22th FRnOG took place in the hotel Intercontinal Opéra in Paris on the 4th of March, 2014.


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Thirty-eight of us met at the Abingdon Well-Being Centre car park on the 6th September before heading over the bridge into Abbey Meadows. Unfortunately it was one of the first evenings that was slightly cooler than the previous few days, which could have had the potential to reduce bat activity (cooler weather equals lower insect activity).
Whilst waiting for bats to appear at Abbey Meadows we went over some basic information about bats, this included: that bats are the only true flying mammals, there are currently 17 resident species of bat in the UK, and that they can be incredibly long-lived for such a small size. We also covered echolocation; this is where bats emit high pitch calls that enables them to produce a ‘sound picture’ which in turn allows them to hunt for food (mosquitoes and moths). Using bat detectors we are able heard these high pitch calls, and by tuning the detectors we are able to tell the difference between most bat species (due to different species emitting at different frequencies). We also went over the five main species that would be expected to be encountered around Abbey Meadows; these were noctule, common pipistrelle, soprano pipistrelle, brown long-eared bat and Daubenton’s bat. Whilst going over this information we were occasionally interrupted by the sharp whistling calls of kingfishers from the River Thames; these may have been birds communicating before going to roost. A tawny owl could also be heard hooting in the distance, possibly from near Waitrose car park.
1 Where calls are around 50kHz these have been noted as Pipistrelle species, as it is not possible to directly attribute the calls to either common or soprano pipistrelle.
2 Identification of Myotis species (of which Daubenton’s bat belongs) can be difficult and it is not always possible to reach species level.

industry_corpus2: Others


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Obsidian Fonts | Hoefler & Co.
A majestic typeface uses digital means to achieve traditional ends.
Decorated typefaces have long been a battleground for technology. In the nineteenth century, steelplate engraving allowed letters to become elaborate, flowery confections, giving rise to a style that lives on in the shaded and curlicued letters of banknotes and diplomas. Type foundries responded to this new fashion by creating ever more intricate printing types, to help printers attempt the same sorts of effects achievable through engraving. Producing these typefaces proved challenging: elaborate hand work was time consuming, resulting in fonts with severely abridged character sets (rarely more than just capitals), and attempts at mechanization produced only “engine-turned” letters with uniform patterns that were bland and unevocative. The nineteenth century would never see a solution to its own riddle of how to industrialize the shaping of letters.
We began the Obsidian project with two questions: can a decorated typeface pay homage to this tradition while being relevant to designers today, and what tools can we create to help us get there? Type design is still largely a manual art, and we felt the acute need for technical solutions to help us both explore our options through rapid prototyping, and execute successful ideas across the massive scale demanded by a contemporary typeface. Not content to be a set of decorated capitals, Obsidian would have 1,400 glyphs spanning both roman and italic styles, bringing its esprit to the most esoteric of punctuation marks and accents.
Having completed work on our Surveyor family, which celebrates the rich traditions of engraved letterforms, we used this work as a foundation for Obsidian. To explore the ways in which a typeface might be decorated, we developed a set of proprietary tools to add highlights to letterforms — ultimately creating a suite of software for interpreting two-dimensional letterforms as three-dimensional objects, through the application of virtual light sources that vary in position, angle, and intensity. Obsidian followed an iterative process, in which the tools revealed not only opportunities for improvement in the code, but in the typeface’s underlying design, and even unexpected virtues that we allowed to reshape the design brief itself. The result is a type family that escapes the shackles of historical style, while honoring the best traditions of decorative typography from the industrial age.
Smart Swashes Obsidian’s swash caps and swash small caps feature built-in intelligence that helps automatically improve the rhythm of text.
Stylistic Sets Obsidian uses an advanced feature of OpenType-savvy applications, allowing designers to transform the look of the font with a single click.
Language Support. Obsidian features our Latin-X™ character set, covering more than 140 languages throughout the world — including all of Central Europe.


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> I hadn't run autogen.sh before configuing. That fixed it.
> >(and probably in some other cases) - it's what generates our makefiles.
In reply to: Dan Christian: "Re: trunk build broken?"


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Particular attention must be given to the design of the die and process parameters to prevent radial drawing stresses and tangential compressive stresses that can result in wrinkles in the material of the flange region of the part.
This process work hardens the metal and creates a seamless finished part that is stronger than the original sheet metal blank. When the depth of the drawn part is greater than half its cross section, it is considered a deep draw.
What are the Benefits of Deep Draw?
Cost Effective – As unit count goes up, cost typically goes down. Since deep draw allows for production of high volumes, this provides a more cost effective solution.
Additionally, in many situations deep draw requires drawing the part through many dies. However, in all the parts with a large cross sectional area made at Meco this process is achieved using one die which saves labor as well as tooling dollars.
Less Waste – Additionally, deep draw produces far less material waste than most machined parts. Less waste means cost savings as well. What’s more, it can replace multi-part components creating a more nimble solution as well.
Time Saving – Another benefit to deep draw is the efficiency created by its secondary operations being performed on the drawing machine. Furthermore, the deep draw process eliminates the need for secondary heat treating, which is another time saving benefit.
Highly Customized – Deep draw is not one size fits all. For example, maybe you need a way to create a lightweight product that can withstand hard use. This method allows you to consider the function required of your end product and create something to meet that need.
Versatile – Sometimes you need to fabricate products that have specific aspect ratios other manufacturing techniques can’t produce. Deep drawing processes often involve complex geometries that may be accompanied by the succession of other press forming techniques such as coining, curling, side piercing and trimming.
Consistent – Finally, the part-to-part and batch-to-batch consistency deep draw affords offers peace of mind when you need to produce in large quantities.
While a popular method used in the manufacturing industry, deep draw is still very complex and requires a great deal of expertise.
The process of deep draw creates a stronger net shape at a lower cost due to reduced waste and can also lead to lower assembly costs. Deep draw can produce precise parts, is very repeatable, and may also be more cost effective than machining, die casting, or metal injection molding.


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You’ve likely heard the old phrase You are what you eat. And when it comes to depression, that may be exactly right, as certain nutritional deficiencies can put you at a markedly high risk of depression.
So let’s look at those nutrients where inadequate intake may adversely affect your mental health, and make some strategies to ensure you get enough – for both your body and your mind!
In particular, we want to look at foods that affect your neurotransmitters; dopamine, norepinepherine, and serotonin in particular are key pieces of your mental health puzzle. Built of amino acids, it should be easy to ensure adequate neurotransmitter health with a balanced diet–but getting a balanced diet isn’t always so easy for everyone.
In particular, deficiencies in the following nutrients can cause real problems with your brain’s chemistry, and as a result, can lead to increased risk of depression.
B complex vitamins all vary, but in general, each can have profound effects on mental health. B12 deficiency, for instance, has been linked to brain shrinkage and dementia (as well as depression). Folate, B6, and B12, help maintain healthy protein metabolism, which decreases the risk of depression. B vitamins may best be found in dark leafy greens, though nuts, seeds, whole grains, and meats can also be good dietary sources.
Iron deficiency, also known as anemia, can result in apathy, brain fog, fatigue, irritability, decreased motivation, and loss of appetite. While more common in women, it can also occur in men, and is frequently misdiagnosed. It can also aggravate any existing depression or other mental health issues. Eating vitamin C rich foods helps increase the absorption of iron, which can best be added to your diet in beef, dark meat chicken, eggs, lamb, liver, oysters, pork, and white beans.
While the average American gets less than half their daily recommended magnesium, the consequences couldn’t be more dire: Magnesium helps reduce anxiety and the risk of diabetes, lower blood pressure, and is required for more than 300 biochemical reactions. It also helps activate the reactions necessary for neurotransmitter production, so not getting enough magnesium can markedly increase your risk of depression as a result. Bran, dark green vegetables, dark chocolate, nuts and seeds, and whole grains are all good sources of magnesium in your diet.
While fatty fish are loaded with omega-3 fats (the good fats!), you can also get them in fortified eggs and in daily supplements (though your body best absorbs those fats and makes best use of them if taken as part of your regular diet). In addition to the part where omega-3 fats are great for neuron function and reducing inflammation (which itself can be a key factor in depression and other mood disorders), the key risk in not getting enough omega-3 fats is that you’ll likely simply replace those good fats in your diet with trans fats, which actually increase inflammation.
Selenium is similar to iodine in that it is necessary for healthy thyroid function, which can have major mental health consequences. The best food sources include Brazil nuts, chicken, fish, ham, liver, and shrimp. Additional benefits of getting enough selenium include it’s anti-inflammatory properties, which can also be helpful in combating depression and maintaining mental health.
While one of the best natural sources of vitamin D is adequate sunlight, that isn’t always an option. Unfortunately, not getting enough vitamin D can lead to increased risk of anxiety, dementia, depression, and seasonal affective disorder (SAD). The best natural food sources available are mostly fatty fish, such as herring, mackerel, salmon, and sardines, though for most people a supplement will be needed if they can’t get enough vitamin D from natural sunlight exposure.
Critical for the production and function of neurotransmitters, zinc is also (like magnesium) involved in more than 250 biochemical reactions necessary for good mental health, so not getting enough in your diet can have major ramifications. It also is important for digestive function and your immune system, both of which have mental health applications; as much as 50% of your dopamine and 90% of your serotonin supplies are produced by in small intestines. Fortunately, there are lots of good zinc food sources, including beef, cashews, chicken, crab, lamb, legumes, oysters, and pork.
At the end of the day, you really are what you eat–and there may be nowhere that this is more true than your brain. If you don’t feed your brain well, you can’t expect it to function at its best, and this is particularly true when it comes to depression. So check your diet closely–and eat up with the above list in mind!

industry_corpus2: Health & Medicine


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Call today, 732-361-4494, Samsung repair to schedule a same day or next day appointment for a small diagnostic fee, cheaper than the industry average (Appliance Blue Book pricing) which goes toward the repair price. Have an experienced Samsung technician service your appliance today 732-361-4494. All Samsung appliance technicians have extensive experience servicing all types of appliances including Samsung Refrigerator, Samsung Oven, Samsung Stove, Samsung Washer, Samsung Dryer, Brand Dishwasher, Samsung Microwave, Samsung Cooktop, Samsung Freezer and Brand Ice Maker. Samsung commercial appliance repair service as well. Same day appliance repair, Samsung appliance installation, ac repair, offering best pricing, affordable pricing, emergency appliance repair and weekend repair. Call now 732-361-4494.
Call today, 732-361-4494, Samsung repair to schedule a same day or next day appointment for a small diagnostic fee.


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Welcome to the Continental Commercial Specialty Tires eLearning!
Get to know the various tire construction types, their features and applications. Extend your knowledge with interactive training modules and become a tire specialist.

industry_corpus2: Automobiles


text: Hilton Head has all kinds of fantastic restaurants… famous for fresh local seafood the Island also offers a multitude of restaurants catering to all cuisines. After a great meal you can look forward to a night on the town…many night clubs and taverns for you to enjoy. Many shops and specialty stores as well.

industry_corpus2: Hospitality & Catering


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The Nations top choice in finding true Wheelchair Vans For Sale. A complete selection of New, Used and Pre-Owned wheelchair vans for sale from top rated wheelchair van dealers. Check our wheelchair vans page for resources on available wheelchair vehicle conversions. Apply for a loan online in just minutes on your wheelchair van.
All the vehicles you see are "For Sale By Owner". Anyone can list their wheelchair van for sale by owner at BLVD.com. These are private sellers who no longer need their van and want se sell it to someone who needs it. They may also be a scammer, make sure you perform your due diligence before buying from a private seller.
- If there is a lien, perform the transaction at the bank whom the lien holder is listed.
Ensure the selling party is the owner.
ALWAYS take possession of the title upon payment.
- You should never make payment without receiving the title.
When buying from a private seller, BLVD recommends you always get a vehicle inspection from a local mechanic you trust. Have the engine and drivetrain inspected for major issues. Always view a copy of the title and ensure it's in the sellers name, does not have a lien and is not classified as "Salvage". Salvage title means the vehicle was at one time considered a "Total Loss" by an insurance company thus destroyed in a major accident. It may have since been repaired, but a fully repaired vehicle is never as good as one that has not been crashed.


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It’s so hard to keep it secret. No one understanding the temptation of such an everyday thing as eating. I just don't understand how other people are not constantly obsessing over every little piece of food they put into their mouth like I do. What is that like? What does it feel like to eat and not feel guilty or to not exercise for less than 2 hours a day and not feel terrible about yourself?
It’s like I live in such an unknown hidden world - so different from everyone around me..
I only wonder how much longer this will go on.
19 year old Stephanie - I hear you. I see you. I love you.
It is easy to feel so alone when you feel so misunderstood.. When you feel like your body is an alien and you don’t know how to trust it. When you feel like you’re searching in every crevasse for some kind of validation.. for someone, anyone to tell you that you are worthy that you are good enough. I know. And it is okay. It is all okay.
You are right where you are supposed to be. This is a part of your journey. You are allowed to love and accept the challenges, the thoughts, the hardships. You are allowed to process the shame, the guilt, the heaviness. You are allowed to feel. You are allowed to be angry.
But just know that you are also allowed to let go. To lean into the pain and know that you can handle it. To know that healing comes from digging deeper, from allowing what is to surface.. Not from numbing the pain.
This will not be forever. I promise. Just keep going.


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Equipped with the latest BMW dealership technology and computer system, we can diagnose any problems or concerns, from minor to major, in a timely manner. Quickly finding electrical, mechanical and fiber optic issues will save you time and money from extended diagnostic charges at the dealership.
Out with the old, in with the new? Sometimes the smartest option for a worn or high mileage engine is a total replacement. We provide you with options such as a low mileage pre owned discounted engine, or start you out fresh at 0 miles with a new one.
Noisy or worn brakes can cause vibrations, unwanted noise and some extreme cases of total brake failure. Have them checked regularly and replaced by our team with high quality BMW replacement parts and fluids, ensuring the safety of you and others while remaining affordable.
Keep your pride and joy running in tip top shape with regular scheduled maintenance. Preventative Maintenance is the key to ensuring your car stays on the road for years to come.
New bushings, struts, and control arms will make your car glide over the road as BMW intended, and take stress away from other undercar components and frame. Fluid may leak from worn seals on shocks and struts the same way as any other seal or gasket on your car. Replacement is necessary if you hear noises or bounce over bumps, or have an unwanted floppy feeling of the car while driving.
We offer full transmission service options from a fluid/filter change, electrical and hydraulic parts replacement, to a full refresh of internal components. We also offer a lot of clutch options for you, from BMW factory original replacements, to clutches designed to handle more than 800 horsepower, and everything in between.
Have a pesky rattle or leak? Maybe you're looking for better performance and fuel economy? Whatever the case may be, we have you covered.
We can find even the smallest leak with our pressure testing equipment. A full coolant flush can prolong the life of your engine, prevent freezing and improve thermal efficiency. BMW recommends a full system flush with OEM blue antifreeze every 4 years or 50,000 miles. All radiators and pumps we get directly from BMW North America at discounted rates.
With the most up to date dealership software and hardware, we can program and code every BMW from 1994-2016. Contact us for a full list of features.
Power hungry? Every car enthusiast loves to modify their engine for more power and efficiency. Take the guess work out of finding the best performance options for your car or prevent worrying about mismatched parts. Give us a call today!
Carbon deposits in your engine can clog your valves and build up on your pistons, reducing power, causing bad fuel mileage, and creating hot spots inside your engine which may lead to premature failure. Injector flushing and manually removing carbon deposits has substantial effects on your engine such as: Better throttle response, better engine idle quality, more power, better performance and increase fuel mileage.
And Much More! Contact us today with any of your concerns or modification needs! We do it all!


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If you would like to donate to the Hanway-Wong family or if you would like more information about the fundraiser I participated in on Sunday, please check out the Facebook page or the GoFundMe page.
My mother used to haul around a fat, cloth-covered binder called a “Day Minder.” It was scribbled over with notes, paper-clipped with lists on scraps of paper, and ridged with ugly tabs. Teenaged me would roll her eyes every time Mom pulled this brute out of her over-stuffed bag to write down a new appointment or remind the family of some forgotten chore. Sure, she was managing the schedule and tasks of five people, but did it have to look so cluttered? Did she really need that many lists?
This is the second of a two-part post. In Part I, I analyzed a brave and powerful story by Lauren Fleshman and discussed how to find the monster–the thing that prevents a hero from accomplishing her goal–in a story. In Part II, I’m hunting one of my own inner monsters.
It’s not difficult to find things I’ve been avoiding in my life. As you may have guessed from this blog, I like taking pictures. But I haven’t posted any pictures of myself for the last year. Why? I’ve had a hole in my mouth.


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In Bucks County, trees and plants may die back during the fall, but the legends never do. In fact, in the fall season, centuries-old tales of ghosts and otherworldly happenings come more alive than ever. After all, the area is rich with history, and spectral rumors tend to come with the territory. Here is a compilation of some places with haunted backstories.
The Inn dates back to the late 1800’s, however the grounds on which it was built already made history as a camping ground for George Washington before the famous Delaware River crossing. This may have implications in the location’s haunted status, but the most well-known phantom is that of a young slave girl named Sarah. Not much is known regarding how Sarah died, but she reportedly stayed at the Inn as part of her route along the Underground Railroad. She is said to appear to other young girls and tell them her story.
Like many places with three centuries of history behind it, this manor is enveloped in legend. Situated along the Neshaminy Creek, it is said this is where Benjamin Franklin conducted his world-famous kite experiment. Not only that, there have been anecdotal reports of ghostly apparitions of a figure flying a kite on rainy nights. In addition, there are also accounts of battle sounds being heard by the trenches surrounding the house. Some say these are otherworldly echoes from the Revolutionary War.
Many people report feeling a bizarre presence or queasiness whilst in the Logan Inn, and given its historical significance, this barely comes as a surprise. This centuries-old landmark has survived the Revolutionary and Civil War, but is reportedly haunted by many soldiers who did not. Some claim to see a Revolutionary War-era figure beating a drum throughout the establishment, while others report seeing inexplicable dancing orbs.
Perhaps the most notoriously haunted part of the house is Room 6, otherwise known as “Emily’s Room," allegedly taking its name after the mother of a previous owner. Reports range from sightings of figures in the mirror to sensations of pressure in the chests of inhabitants while they sleep, often times resulting in guests deciding to prematurely end their stay.
A 250-year-old Victorian mansion, the Pen Ryn is enshrouded in ghostly mythos. The house was once owned by a British-supporting family, whom had become reclusive after the Revolutionary War. The son of the family, Robert, was said to have fallen in love with a woman who opposed British rule. This infuriated his father, who promptly forbade them from seeing each other. As legend has it, an emotionally distraught Robert then waded out into the river where he drowned. He and his lover are said to haunt the grounds, making ghostly appearances around the fall and winter seasons.
This hotel is what some may consider the “crown Jewel” of haunted locations in Bucks County. It has become associated with many different ghostly legends, notably the “Woman in White," who has been seen wandering the halls as well as sitting in a guest room holding a revolver. According to legend, this is the ghost of a woman who found her cheating husband in a room with his mistress. Embroiled with vengeance, the woman then killed them both and then turned the gun on herself. Witnesses claim that her apparitions are accompanied by the smell of lavender.
This tavern in Yardley regales the community with food and drinks, but also tales of its haunted history. The pub was established in 1864, served as a stop along the Underground Railroad and also bore witness to two murders within its lifetime. Spine-tingling reports of the paranormal by the staff of the tavern are exchanged as casually as hellos, just to give an idea of how strong the spiritual presences are here. The Continental also generally hosts events in the Halloween season, so stay tuned to see what's in store this year.

industry_corpus2: Travel & Geography


text: This October, an Amazing Race will take place at The Reef. Get your best team together and useful supplies ready for the big event. Winners will come away with some fantastic prizes!


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The laboratory carries on experimental and theoretical studies on ionizing radiation effects, with applications in the clinical use of radiation for diagnostics and therapy (including the risk of complications and secondary tumours), radiation protection, and also for manned missions in deep space.
In particular, the ultimate goal is to shed light on the fundamental mechanisms leading to damage at sub-cellular, cellular, tissue, organ and systemic levels, starting from the way in which physical interactions (track structure) deposit energy in the target. The radiation induced DNA damage and repair processes (and their relevance in inducing other biological endpoints) are investigated, along with intra- and extra signalling perturbation (bystander effect), and their anti- and pro-carcinogenesis implications. Ionizing radiation needs to be analyzed as a perturbing agent of a complex system that will react with complex behaviours and feedback phenomena, and may end up with a homeostatic equilibrium or with a pathological condition. Classical reductionist studies are combined with system, multi-scale approaches (systems radiation biology), also to integrate datasets on different radiation effects (e.g. pro-inflammatory responses, cell senescence).
§ to use radiation as a probe to study the response of biological systems to external stimuli, e.g. in samples from patients with (rare) genetic diseases.
§ to assess the risk and develop countermeasures for missions in open space (e.g. mission to Mars).

industry_corpus2: Technology & Research


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Q&A: What makes the World Cup soccer ball special?
A 28-foot giant squid is presented in the London Natural History Museum. Although previous specimens had been fished up or found on the beach, researchers have never filmed a live giant squid in its natural habitat until now. Courtesy of Discovery News.
Among the greatest mysteries of the deep sea is that of the giant squid. Ever since Norse mythology popularized it as the Kraken, this little-understood creature has become an exaggerated symbol of terror and destruction at sea, lurking in the background of countless stories and movies. But finally, after years of elusiveness, a Japanese research team finally captured the giant squid on camera in its natural habitat last July.
In conjunction with the Discovery Channel, the research team observed the mammoth squid in action for the first time in history. Almost six years of research culminated in an 18-minute glimpse on camera. As the four-meter-long creature with “razor-toothed suckers and eyes the size of dinner plates” peered into a small submersible containing a pilot, scientist, and photographer, the excitement was incredible. “That’s what got me into science in the first place — this opportunity to explore a new frontier,” Edith Widder, one of the research team members, told NPR.
Researchers were surprised to find that the giant squid was a metallic color that varied between silver and gold. Courtesy of Fox News.
Past attempts at viewing the squid in its natural habitat involved cameras, lights, and equipment noise, and such technology had scared the creature away. Another team had fished a giant squid out of the ocean in 2006, but the creature quickly died on the hook, precluding live observation. This time, at the crushing depth of approximately 2000 feet, the team lured the squid to their location using a concoction of squid pheromones and LED lights. These lights were used to imitate the atolla, a small jellyfish that lights up in response to its larger predators. The squid was naturally attracted to this light because it feeds on the atolla’s predators.
In addition to these methods, one of the most innovative techniques that the researchers employed was their use of a near-infrared (NIR) light, which is not in the spectral range of either humans or giant squids. As a subset of infrared (IR) light which ranges between 800 nanometers and one millimeter, near-infrared light ranges between 800 nanometers and 1,500 nanometers and can only be detected by humans with a specialized camera.
With eyes the size of basketballs, the giant squid can detect predators from 120 meters away. Thus, equipping the submersible with near-infrared light was essential for observing it at close range. Courtesy of Norbert Wu.
“Typically the operating wavelength of a camera is determined by the material used to convert photons to electrons,” said Dr. Brandon Redding, a postdoctoral researcher in optics in the Yale Applied Physics Department. “For instance, NIR cameras are often fabricated using indium gallium arsenide rather than the silicon used in most visible wavelength cameras.” Although commonly used digital cameras have receptors that are sensitive to both visible and IR light, a filter blocks out most of the IR light detected. NIR cameras essentially achieve the opposite by utilizing a special filter to block out visible wavelengths while allowing the IR light to pass through.
As a figure in Norse mythology, the Kraken was commonly depicted as a marine threat that would engulf ships and terrorize sailors. Courtesy of Angelfire.
The team’s success is a big step for deep-sea research because its procedures can be adapted to observe other creatures with spectral ranges similar to that of the giant squid. This particular camera worked in the desired optical range that allowed peaceful observation of the squid, but other cameras can be built for filming other creatures as well; the potential for discovery using stealthy observation techniques is enormous. According to Widder, only 5 percent of the ocean has been explored; furthermore, that small fraction has been observed through the use of intrusive cameras and bright lights.
Exploring the other 95 percent of the ocean is an exciting prospect and could very well transform our understanding of marine life altogether. “The reason we know giant squids exist is that they happen to float when they die,” said Widder. “So what about the stuff that doesn’t float when it dies?” Perhaps the “Kraken” is only the first of numerous sea creatures that have yet to be demystified.


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Network traffic collection can be disabled completely by providing corresponding launch flags. Refer to configuration and look for monitorNetwork launch option for more info.
Bugsee captures network activity from the application and stores headers and in some cases body of the request and response. In order to allow you to hide user identifiable and other sensitive data from these network logs, we let you hook into network capturing by installing network filter handler that will be called for every event about to be recorded.
For every event to be recorded, Bugsee will call your method and provide you with an object containing captured data. It is your method's responsibility to clean up all user identifiable data from that structure and return it back to Bugsee.
The handler is going to be called several times for each network request, depending on its life-cycle. Usually for successful requests its going to be called twice, once with the request event (request headers and body) and once after completion and will contain headers and body of the response.
body Body String NO Raw body of the request or response where available.
headers HTTP Headers Object NO Key-value map of HTTP headers associated with the event.


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Looking For A Garage Doors Installation White Rock Canada At DoorSmithBC LLC, we provide a huge variety of garage door products to supply any and all residential or commercial needs. We only carry supplies in the highest level of quality available so that your home or business can rest assured that we’ve done the job right every time. We work with well-known and renowned dealers to install and repair garage doors in the White Rock Canada area. Call us today at (778) 927-2950 to speak with one of our highly qualified installation experts to learn more.
Our line of residential garage doors is built to last through years and years of use while adding beauty and charm to your property. We offer a multitude of attractive garage door solutions that are strong enough to weather the coldest winters as well as the hottest summers. Our products will add aesthetic appeal to your home while protecting you and your home from any and all elements.
At DoorSmithBC LLC we strive to complete your garage door installation safely, professionally, and perfectly. It’s crucial to have peace of mind in knowing that your garage door is installed properly. We have a long list of satisfied customer reviews to demonstrate our tireless commitment to excellence. Call us today at 778 927-2950 to learn more about scheduling an installation or to get a free estimate on your project.
The sad truth is that some companies will say nearly anything to get your business. They perform a shoddy job. Then, in a few weeks to a few months, you are facing a need to repair or replace the entire system. At DoorSmithBC LLC we care about each of our clients and pride ourselves on excellence in service, dependability, and reputation as the premier choice for garage doors installation White Rock Canada.
While there are many projects you can complete easily on your own, installing garage doors is not one of them. This is a large task that requires specialized equipment, tools, and expertise. You want to ensure that the doors are perfectly installed to avoid accidents or injuries. An improperly installed door could quit working or even fall causing property damage or hurt you or a family member. By trusting us, you can rest assured that your garage doors will be installed safely and properly. Call us today at (778) 927-2950 for more information and to schedule your free estimate.
We are available to you 24 hours a day and seven days a week since you can’t plan out when you’ll need to find a reputable garage door installation technician. If you are faced with garage door issues or any locksmith needs DoorSmithBC LLC is here to help. We offer great rates and same day service for our highly valued customers. Call us at (778) 927-2950 to schedule an appointment or speak to one of our highly trained experts.

industry_corpus2: Real Estate & Construction


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EL RODEO, GUATEMALA - The death toll from a volcanic eruption in Guatemala rose to 69 on Monday as family members desperately searched for the missing in makeshift morgues and on streets blanketed with ash.
Guatemala’s national disaster agency, CONRED, increased the death toll as more bodies were pulled from the debris around the village of El Rodeo, which was hard hit by the eruption. Just a fraction of the victims have been identified so far.
At a makeshift morgue in the city of Escuintla, about 30 km (18.6 miles) from the explosion, distraught family members came to search for their relatives among the dead.
Francisco Quiche, a 46-year-old welder, gave a blood sample to try to identify his son’s body, though he already knew his son’s fate.
After evacuating the town of El Rodeo with his family, he returned to search for his son and daughter-in-law. Peering through a hole in the wall of his son’s home, Quiche saw the boy’s body. He fears his daughter-in-law is dead as well.
The eruption of Fuego - Spanish for “fire” - on Sunday was the biggest in more than four decades, forcing the closure of Guatemala’s main international airport and dumping ash on thousands of acres (hectares) of coffee farms on the volcano’s slopes.
By Monday evening, the volcano’s activity was lessening, and is expected to continue to diminish in the coming days, Eddy Sanchez, director of the seismological, volcanic and meteorological institute Insivumeh, told reporters.
The task of retrieving bodies on Monday was hindered by another eruption and an apparent landslide on the southern slopes of Fuego triggered fresh evacuations. Later in the afternoon, heavy rains forced rescuers to abandon the search in El Rodeo until the next morning, a spokesman for CONRED said.
Rains are expected to continue to complicate searches in the coming days, Sanchez said.
Structures and trees at the base of the Fuego volcano were completely coated in brown and gray.
Armed soldiers donning blue masks kept watch at a badly affected neighborhood that had been cordoned off, Reuters photos showed. As late as Monday afternoon, the volcano continued expelling a dark cloud of gases and rocks.
Fuego, one of several active volcanoes out of 34 in the Central American country, is near the colonial city of Antigua, a UNESCO world heritage site that has survived several volcanic eruptions. The latest activity is mostly on the far side of the volcano, facing the Pacific coast.
The eruption on Sunday sent columns of ash and smoke 6.2 miles (10 km) into the sky, dusting several regions with ash. More than 3,200 people have been evacuated, CONRED said.
CONRED shared a photo showing the flows of gas and mud sweeping down a mountainside and across a broad valley, engulfing a small village.
The eruption showered sand and ash on coffee plants across as much as 6,890 acres (2,788 hectares), including close to the volcano’s cone, causing an estimated loss of 0.91 percent of Guatemala’s coffee production, the country’s national coffee association said.
In some areas, rain rinsed ash off the leaves, and the full extent of the damage was not yet clear, the association said.

industry_corpus2: Power & Energy


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"On August 14, Julius Chambers, a reporter of THE TRIBUNE, was consigned to Bloomingdale Lunatic Asylum by regular process of law, and was placed by the Assistant Physician in charge in the wards for excited patients, being thought a dangerous maniac. At the end of the week he appeared (by instruction of this office) to be so much improved that he was removed to the ward for quiet patients, and encouragement was held out by the same physician that in six or seven weeks he might be discharged. On Saturday last, after a write of habeus corpus for his release had been served, Dr. David T. Brown, Superintendent of the institution, talked with him for an hour or two, and, being familiar with the disease which he simulated, at once saw the reporter was sane. On Monday, at the earnest solicitation of the physician and the legal adviser of the Asylum, consent was given that he be released without further public legal proceedings. Yesterday, however, Mr John D. Townsend, in whose name the application for release was made, explained in the Supreme Court his connection with the case and the fact that the person committed was a reporter for this paper.
"The reporter's story of his incarceration in the Asylum will be told in detail in tomorrow's TRIBUNE, accompanied by his sworn affidavid of the truth of all he states.
"In making this investigation of this institution, THE TRIBUNE was prompted by no motive of idle curiosity, no purpose to misrepresent, no object other than xxxxxx correct way, and in a manner which would satisfy and convince the public. Its examination was made on a fixed and carefully elaborated plan to test the legal issues involved, and the truth of the charges previously put forth by former employes of the Asylum. To have bribed two physicians to certify falsely his madness would have been to prove only tht there were rogues in the profession; hence it was decided to feign insanity and test the scientific knowledge of the committing physicians. . . . It was charged that strangers to patients sometimes committed them. It was therefore decided that absolute strangers should be employed. It was said that police justices committed men without examination. The Justice who sent our reporter to Bloomingdale never saw him at all, and does not know the names of the persons or physicians who made the application . . . The detailed story of those adventures to be told by the reporter will be a plain, unvarnished tale, without reservation of names or facts, and we are sorry to say that it will be adverse to the institution, and reflect painfully on the law of commitment and its administration in this city."
Description: Curtain-raiser and explanation for the undercover investigation of the Bloomingdale Lunatic Asylum by reporter Julius Chambers, to be published August 31, 1872.

industry_corpus2: Law & Justice


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Also known as "Waggoner Frocks," Work Smocks were often worn by the 18th century working class as an outer garment to protect clothing from being soiled. These articles are well documented by Moreland and Diderot, as well as in period art. Oversized, roomy, and long. 10" longer than our workshirts with 14" side slits for improved mobility. Also available in osnaburg. This also makes an excellent night shirt. Available in sizes XS to XXXL.
Call for availability. Please allow 1-3 weeks if garment needs to be made.


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WASHINGTON--An unusually diverse alliance of private-education and religious groups that banded together to support a Bush Administration proposal on private-school choice will continue to promote the idea, despite the Senate's defeat of the proposal last week.
In addition to several Roman Catholic religious and education organizations that have long favored private-school choice, the lobbying coalition includes some private-school groups that, until now, have not forcefully supported federal aid for a choice plan that included private schools.
"This does represent an evolution over 10 to 12 years in our board's thinking on what constitutes an acceptable choice proposal," said John W. Sanders, the vice president of the National Association of Independent Schools, which represents most of the nation's leading independent day and boarding schools.
The N.A.I.S. has previously supported school choice generally, but has shied away from the more contentious idea of allowing the government to give money to parents who enroll their children in private schools.
The choice amendment introduced by Senator Orrin G. Hatch, Republican of Utah, "seems like a proper experimental vehicle" because it would provide aid to low-income families to send their children to private schools, Mr. Sanders said before the Senate took its vote late last week.
Twenty nonprofit religious and education groups formed the National Coalition for Improvement and Reform of American Education this month to support the private school choice amendment to S 2.
The groups represent virtually all segments of private education, including independent, military, Montessori, Catholic, Jewish, Lutheran, Episcopal, Seventh Day Adventist, Quaker, and evangelical Christian schools.
"We feel the coalition allows us to show the diversity of support among ,the private-school associations," said Joyce McCray, the executive director of the Council for American Private Education, the umbrella organization representing most of the private-school groups.
Despite the defeat of the choice amendment, the coalition will stay in place for now to promote other private-school choice proposals, said Greg Kubiak, the government affairs director for CAPE.
The potential political impact of the new coalition was underscored last week when several private-education leaders were called to the White House to meet with key Administration officials, just as the Senate was beginning debate on the education-reform bill.
Representatives of the coalition met on Jan. 21 with, among other Administration officials, Samuel K. Skinner, the White House chief of staff; Secretary of Education Lamar Alexander; and Roger Porter, the President's domestic-policy chief.
"This was a fairly straightforward meeting to clear up any questions we had about details in the proposal," said Mr. Sanders of the N.A.I.S., who attended. "We wanted to know how seriously committed the Administration was" to the private school choice demonstration project.
"There is no point to having the private-school community go out on a limb if we are not getting support" from the Administration, he added.
The coalition has sent a letter and position paper to each senator this month that seek to answer criticisms that have been leveled against the idea of federally funded private-school choice.
"If there is anywhere in which the public system is failing and the private schools are succeeding, it is in the highly concentrated low-income communities," the position paper says in support of the proposed demonstration program, which would provide a total of $30 million for up to six projects in which low-income families would get certificates to send their children to private schools.
In addition to CAPE and the N.A.I.S., the coalition includes: Agudath Israel of America, the American Montessori Society, the Association of Military Colleges and Schools of the United States, Catholic Daughters of America, Catholic Golden Age, and Christian Schools International.
Also, the Evangelical Lutheran Education Association, the Friends Council on Education, the Institute for Independent Education, the Jesuit Secondary Education Association, the Knights of Columbus, the National Association of Episcopal Schools, and the National Association of Private Schools for Exceptional Children.
Also, the National Catholic Educational Association, the National Council on Catholic Women, the National Society of Hebrew Day Schools, the Seventh Day Adventist Office of Education, and the United States Catholic Conference.

industry_corpus2: Subject Education


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If you’re in a hurry, here are the slides for our talk.
Help Design The First Annual Rocky Mountain DataCon!
The Boulder/Denver Big Data Meetup has been serving the Colorado big data community for 5 years. This Fall, we want to mark the occasion by putting on a full conference dedicated to Big Data.


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The Charles Redd Center for Western Studies at Brigham Young University invites applications for its Visiting Fellow Program in Western Studies each academic year. University faculty of all ranks, independent scholars, freelance authors, and other public intellectuals who are working on a significant article- or book-length study are eligible to apply for this position. The Visiting Scholar may be in residence for two to four months during either the Fall Semester (September–December) or the Winter Semester (January–April). The Center will provide a stipend of $2,500 per month of residency, office space, a networked computer, campus library and activity privileges, and limited photocopying and printing. Upon request, the Center will provide a part-time research assistant.
4) The names and contact information for two references.
Applications must be postmarked by the deadline of March 15.
Incomplete applications will not be considered. Announcement of the awards will be made by May 1. Award recipients will be required to submit a one-page report of work completed by October 15 of the following year.
Visiting Fellows enjoy the luxury of time away from heavy teaching loads and other responsibilities so that they can focus almost exclusively on their research and writing. Visiting Fellows fully participate in the intellectual life of the Center and the University. During their time at BYU they give a public talk on their research and lead a seminar session with interested faculty and students. They also make themselves available for a small number of guest presentations to BYU classes on their research.


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As Editor in Chief of Southern Seasons Magazine, I get to interview the most fascinating people in the world! I invite you to subscribe to or advertise in our glorious luxury lifestyle magazine to reach the most affluent readership in the South.
From Asia to the Arctic, the Amazon to the Middle East, Vivian has journeyed far and wide on her globetrotting adventures. An award-winning and widely published travel writer, she has covered the glamour of the Cannes Film Festival and the excitement of the Monaco Grand Prix.
An Atlanta-based multi-media journalist, editor and author, Jennifer is a knowledgeable gourmet “foodie” who spent years in the topflight restaurant biz. She loves exploring the city’s restaurants and sharing her finds with Southern Seasons readers. She recently co-authored “Make it ZERO,” a hopeful social justice book.
Both Wendy Warren and Jody Williams are wives and mothers who simply love to entertain and prepare sensational meals for friends and family. Frequently flying across the country to visit, they begin at the food markets and end up in the kitchen together creating delicious meals that are full of flavor, healthy and easy to prepare.
Southern Seasons Magazine has no connection or affiliation with any other magazine, catalog, Web site, store or product with the words “Southern” or “Seasons” in their title.
Hey Buddy!, I found this information for you: "About Us". Here is the website link: https://southernseasons.net/about-us/. Thank you.


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Promotional mugs have always been one of the most demanded products within the range of promotional merchandising products. At BestBranding, we take the usual advertising mugs to a new dimension.
Why Are The Customised Mugs of BestBranding So Special?
BestBranding’s customised mugs have all the features that a good product should have. They offer perfect coverage of the main objective for which these advertising mugs are made and, in addition, are offered with a good quality product.
At BestBranding, we do not try to offer just good advertising through a logo on a promotional mug. We understand that for the item to be effective and not only should the advertising support be adequate, but there should be high-quality products offered.
Our cheap BestBranding promotional mugs have a wide variety of uses. Actually, they are one of the most integral elements that exists in the field of marketing. They cover all advertising and merchandising needs in one item.
There are many promotional products, but advertising mugs have a double advantage. In the first place, they are objects that are positioned in spaces that are usually visible. As a consequence, the logo, phrase, data, etc. that appears on them is highly visible. There is also another clear advantage of promotional mugs. As a product that is used daily by people drinking in them, a kind of intimacy with the product is generated that makes that what is printed on them also more internalized by the users.
One of the clear advantages of acquiring promotional mugs at BestBranding is the completely customised treatment that we offer to each and every one of our clients. We make buying our products easy. And besides, it's easy, economic, and always has the highest quality and security.
Betting on BestBranding is betting on the quality of the services and the products offered. Choosing BestBranding is choosing a company that automatically puts the client at the centre of all its operations. We always provide the best advice, the best options, and the best advertising mugs available.


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This review was last updated on April 20th, 2016.
Jungle Disk is one the premier backup services in the cloud based services industry, they specialize in security and data backup for businesses. As they say “Backup is all we do, so backup is what we do best”. They offer multiple plans for businesses depending on team size and needs.
They offer pay per month plans with no long term contracts which is appealing for businesses who may be looking to test the service. The plans are offered in two systems; the Jungle Disk plan for protection against your corporate computers and the Jungle Disk Server plan for unlimited server backups on demand.
The basic plan starts at $4 monthly per user and storage fees, this plan is very good value for money. The second plan they offer is their server plan, this plan starts at $5 monthly per user and storage as well. Each user is provided with 10 GB storage free with the initial account, the scale the amount of storage they provide you with depending on your needs. This is efficient from a business perspective as not all employees will need the same storage, this means that the service they provide can save you money on costs as you can scale the amount of storage you provide depending on their respective needs.
Jungle Disk offers unique backup vault features, Legacy backup features, sync folders features and a backup reporting overview. Backup vaults are storage containers within an online disk where your backup data resides for one single computer. This backup vault allows for black-level data de-duplication within and across multiple files and versions of files as well as compression for all data; this means greatly improved backup speeds and less total data stored, each account can have multiple online disks with multiple backup vaults although you can only attach a backup vault to a single computer.
The Legacy backup feature they provide allows you to keep files and folders to your local machine backed up automatically offsite to your Jungledisk, they recommend using their backup vault service though as backup vaults help to keep your overall storage and bills lower. Their sync folders feature is a powerful tool you use to keep a set of data on your network drive and your local computer in sync, it’s useful for example when you need to sync your folders on the go or if you want to keep a folder in sync across multiple computers for your employees or coworkers. Their backup reporting overview feature is both a section in their online control panel for viewing logs and a way of keeping track of your backup jobs by receiving notifications of those jobs.
Security is where Jungle Disk really differs from the competition. They offer an encryption key at sign up for the user that only you know and have access to. This means that even the servers and the team at Jungle Disk can’t see your data without the key. The service they provide means essentially you have control over the access of your files. This also secured by an AES 256 bit encryption layer, this means using their service is even safer to transmit important files.
JungleDisk has its merits when it comes to the speed of their service. I was able to transfer a rather large video file (135MB) within 23 minutes, which is fair considering that I’m using a slow Internet connection. My ADSL line only has 5Mbps download and 1Mbps upload bandwidth. Of course, if you have a faster Internet connection, your transfer times will be many times faster. The problem is that many users still don’t have the latest and greatest Internet connections (like a gigabit connection, for example). If you do have a slow Internet connection, JungleDisk is a good option since their speeds aren’t heinously slow. Some users simply can’t use a service with local encryption since it makes file transfers drag on for hours, but JungleDisk performed pretty well compared to other providers.
The great thing about Jungle Disk is that the service they provide gives you the ability to backup anything and everything you need to keep an extra copy of. You can backup company assets on devices like laptops, desktops and of course servers. Whether the files are videos, photos or document based file formats. Even better, one of Jungle Disk’s best features is the fact that they places zero limits on file sizes for backups, meaning you can back up files of any size. Server plans are available for automated server backups to provide you peace of mind and ease of use.
Of course at any time you can restore any and all files that have been backed up to your Jungle Disk account. The great thing in this case is the user control the access so anytime you need to get your data your unique key gives you access to all your backups, this means that you can so can personally restore the files you need to.
Their site offers great a help center filled with FAQ’s, troubleshooting techniques, and more information when it comes to common questions on the service. This help center is filled with commonly asked questions on problems you may encounter with their service. If there help center does not provide you with the information you need, they also provide a contact form for more specific questions. You’ll notice however their service doesn’t offer any other means of contact such as a phone line or any form of live chat service, this is one of the limitations of the service they provide as instant help to queries or problem with their service can be crucial to businesses, but we expect the turn around time in case of data loss or emgency to be very quick.
At the end of my overview, Jungle Disk sticks true to their word and focuses on only backup for business data. Offering high levels of security with the unique encryption key which puts the access power in the user’s hands. Coupled with their affordable starting plans makes it’s highly appealing to businesses of multiple sizes. If you’re looking for a straight forward backup solution to keep your employees and corporate computer data secure and safely backed up, Jungle Disk will meet those needs.


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We have been enjoying pancakes for breakfast every Sunday for the last couple of months. Maybe it has something to do with being smothered in Butter and Maple Syrup, with a few Blueberries mixed in. They just go so well with all those Sunday Snowstorms that are also being served up every week as well. A hearty breakfast, then go out and shovel the snow.
This week it looks like some moisture will again be falling from the sky. I just hope its all rain for a change. The recipe for this weeks pancakes is also going to change a little. This one looks real good and will be enjoyed for the Sunday’s special. With Blueberries of course.
On the flip side, People with low IQs are more likely to consume higher amounts of alcohol than those with higher IQs, a new study has claimed.
Blessed are they who see beautiful things in humble places where other people see nothing."
To know the value of generosity, it is necessary to have suffered from the cold indifference of others."
They say that your eyes are the window to your soul. When others look into them, your true character will come tumbling out. It's true that you can tell a lot about someone from their eyes.
The first green flag of the NASCAR season has dropped and tempers are flaring, but in the end there was the classic follow up with “Sorry Friend”.
Connecticut native Joey Logano, driver of the #22 Shell Pennzoil Ford won his first career Daytona 500 on Sunday. The Team Penske driver led 31 laps and took the lead for good on Lap 191. Logano wasn't among the favorites coming in to the 2015 Nascar Season opener; the Hendricks cars dominated the race for most of the day. But as the laps counted down, he showed that he could hang with the big boys. By the end, they were left chasing him and never caught up. He now Joins Pete Hamilton, a native from Dedham, Massachusetts, who drove that iconic winged Plymouth for Petty Enterprises in 1970 to become the second New Englander to win the Great American Race.
How little has changed since this speech was first made by Charlie Chaplin. It's from the film “The Great Dictator” which was made in 1940.
Not again! Early this week the Wienermobile lost control and smacked into a pole. I believe I know what happened and I'm sure that ketchup was responsible.
After the Brawl this week at Maverick station in East Boston, I suggest that going there to pass out the Optimism Tickets would be a much needed place to share a little of that Goodwill.