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We assessed whether excessive daytime sleepiness was associated with coronary plaque phenotype and subsequent adverse cardiovascular events.
Prospective cohort study. Intravascular ultrasound (IVUS) examination of the culprit coronary stenosis was performed. The Epworth Sleepiness Scale (ESS) questionnaire was administered, and the patients were divided into 2 groups—(1) sleepier and (2) less sleepy—based on the ESS score. Adverse cardiovascular outcomes were defined as cardiac death, myocardial infarction, stroke, unplanned revascularization, or heart failure admission.
One hundred seventeen patients undergoing urgent or non-urgent coronary angiography were recruited. Compared with the less sleepy group (ESS ≤ 10, n = 87), the sleepier group (ESS > 10, n = 30) had higher serum levels of total cholesterol and of low-density-lipoprotein cholesterols (p < 0.05 for both). The IVUS examinations indicated coronary stenoses were longer in the sleepier group than in the less sleepy group (p = 0.011). The cumulative incidence of adverse cardiovascular events at 16-month follow-up was higher in the sleepier than the less sleepy group (12.5% versus 6.9%, p = 0.03). Cox regression analysis adjusting for age and smoking showed increased hazard of adverse cardiovascular events in sleepier group as compared to less sleepy group (HR = 3.44, 95% CI 1.01-11.72).
In patients presenting with coronary artery disease, excessive daytime sleepiness based on ESS > 10 was associated with longer culprit lesions and future adverse cardiovascular events.
Lee CH; Ng WY; Hau W; Ho HH; Tai BC; Chan MY; Richards AM; Tan HC. Excessive daytime sleepiness is associated with longer culprit lesion and adverse outcomes in patients with coronary artery disease. J Clin Sleep Med 2013;9(12):1267-1272.
Excessive daytime sleepiness is a prevalent health problem that affects 18% of the general population in the United States.1 This condition increases the risk of road traffic accidents and causes serious economic consequences due to poor work performance.2,3 In the clinical context, excessive daytime sleepiness is a common but nonspecific symptom that accompanies neurological, psychiatric, kidney, and cardiopulmonary disorders. Excessive sleepiness is also a side effect of certain medications and a consequence of insufficient sleep duration. The pathological consequences of excessive daytime sleepiness are complex and remain incompletely understood. Previous epidemiological studies have found that elderly people who reported having frequent excessive daytime sleepiness had a higher risk of subsequent adverse cardiac and cerebrovascular events than those who reported never having excessive daytime sleepiness. This pattern remained evident even after adjusting for confounding factors.4–7
Current Knowledge/Study Rationale: There are limited data on the prognostic implication of excessive daytime sleepiness in patients with coronary artery disease. In this prospective observational study, we determined the association between excessive daytime sleepiness (ESS > 10), coronary plaque phenotype, and subsequent adverse cardiovascular outcomes.
Study Impact: The patients were classified into sleepier and less sleepy groups according to their baseline ESS scores (> 10 versus ≤ 10), and we found that the sleepier group was associated with longer lesion lengths. After adjusting for potential confounders, the hazard of adverse cardiovascular events was 3-fold in the sleepier as compared to the less sleepy groups.
In most of these previous studies,4–6 excessive daytime sleepiness was self-reported as a qualitative variable, and some degree of misclassification or overlapping with fatigue could not be excluded. The Epworth Sleepiness Scale (ESS) was developed more than 20 years ago to gain a more objective measure of sleepiness, and is now the most widely used measure of excessive daytime sleepiness.8 The ESS is frequently administered to patients to estimate their risk of obstructive sleep apnea and thus guide decisions regarding overnight polysomnography. The questionnaire also enables the evaluation of responses to treatment for patients diagnosed with obstructive sleep apnea. The ESS has been validated against in-laboratory polysomnography on community individuals in general practice settings.9,10
However, it remains unknown whether excessive daytime sleepiness, as measured by high ESS scores, can predict adverse outcomes in patients with cardiovascular conditions. In this prospective observational study, we determined the association between excessive daytime sleepiness (ESS > 10), coronary plaque phenotype, and subsequent adverse cardiovascular outcomes in a cohort of patients presenting with symptomatic coronary artery disease. Specifically, we targeted patients in whom a stenosis was detected by coronary angiography so that an intravascular ultrasound (IVUS) catheter could be used to assess their plaque phenotype.
This prospective study was conducted at 2 tertiary centers (the National University Heart Centre and Tan Tock Seng Hospital) in Singapore between February 2011 and March 2013. The participants were selected from among patients aged 21 years and older who were undergoing coronary angiography for stable coronary artery disease or acute coronary syndromes, including myocardial infarction with or without ST-segment elevation, and had been found to have ≥ 1 significant (> 50% visual estimation) de novo stenosis in a native coronary artery. Criteria for exclusion from the study included known obstructive sleep apnea (based on previous polysomnography), cardiogenic shock (systolic blood pressure < 90 mm Hg), chronic renal failure with dialysis treatment, previous treatment of the target vessel, being a foreign patient who could not attend the outpatient clinic for follow-up, or inability to provide informed consent. The angiographic exclusion criteria were angiographically visible residual thrombus despite thrombus aspiration or thrombectomy, a heavily calcified lesion, a tortuous vessel, chronic total occlusion, a significant left main lesion, or a distal lesion that was too small to accomodate an IVUS catheter. The National Healthcare Group Domain Specific Review Board approved the study's research protocol (reference: C/2010/00341), and informed consent was obtained from the subjects. Recruited patients underwent IVUS examination of the culprit lesions. During the same hospital admission, the ESS questionnaire was administered to the patients to determine their degree of excessive daytime sleepiness. A flow chart of this study is shown in Figure 1.
Study flowchart
(more ...)
Consenting patients were formally enrolled into the study after identification of the culprit lesion by coronary angiography. A guiding catheter was used to selectively cannulate the ostium of the target coronary artery. Immediately after advancing the guidewire, but before balloon predilation, a 20-MHz, 3.5-French phased-array IVUS catheter (Eagle Eye Gold, Volcano Corp., Rancho Cordova, CA, USA) was inserted into the mid- to distal segment of the target coronary artery. The IVUS catheter was automatically pulled back to the ostium of the guiding catheter using a motorized pull-back device at a speed of 0.5 mm/s (R-100 Pullback Device, Volcano Corp.). All images were recorded in digital format on a DVD for subsequent offline quantitative analysis by 2 investigators (CHL, WH), who were blinded to the ESS data. Any discrepancies between the analyses of the 2 investigators were resolved by consensus.
Conventional gray-scale quantitative IVUS analyses were performed according to the IVUS expert consensus document.11 The following parameters were measured in the culprit lesions in the target coronary artery: (i) external elastic membrane area (mm2), (ii) minimal lumen diameter (mm), (iii) minimal lumen area (mm2), and (iv) plaque burden (mm2).
The virtual-histology-IVUS images were analyzed according to the published guidelines to determine the tissue composition of the lesions.11 The 4 virtual-histology-IVUS plaque components were color-coded and displayed on the virtual-histology-IVUS console, with fibrous tissue shown in green, fibro-fatty tissue in light-green, dense calcium in white, and the necrotic core in red. Volumetric measurements using Simpson's rule were performed over the entire region of interest by tracing the external elastic membrane and the lumen border. The volumetric values for each of the 4 plaque components and the culprit lesion plaque volume were then automatically calculated using VIAS 3.0 offline analysis software (Volcano Corp.).12 Thin-cap fibroatheroma was defined as a plaque with > 10% confluent necrotic core, with > 30 degrees of the necrotic core abutting the lumen in ≥ 3 consecutive frames.13
Patients presenting with ST-elevation myocardial infarction were treated with urgent percutaneous coronary intervention. These patients were not only under time pressure, but were in pain and distress, and may have been medicated with opiates that affect decision-making. To standardize the protocol, the ESS questionnaire was administered to all patients after the angiography and intervention procedures. The recruited patients were approached by a dedicated research assistant and asked to complete the ESS questionnaire in the cardiac ward. The ESS is a validated questionnaire that asks subjects to rate their likelihood of falling asleep in several common situations. In this questionnaire, patients rate their perceived likelihood of falling asleep in 8 everyday situations, and their answers give a score of between 0 and 24 points. Based on the ESS score, the recruited patients who completed the ESS were divided into either (1) the sleepier group (ESS > 10) or (2) the less sleepy group (ESS ≤ 10).
The following demographic and clinical information were collected prospectively: ethnicity, gender, age, height, weight, body mass index, clinical presentation (such as ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina, or stable angina), cardiovascular risk factors (such as smoking, diabetes mellitus, hypertension, hyperlipidemia, or family history of premature coronary artery disease), previous cardiovascular conditions (such as previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery), laboratory investigation results, and detailed angiographic findings.
After hospital discharge, all of the recruited patients made regular visits to an outpatient clinic. The physicians conducting the outpatient clinic were not part of the study team, and were blinded to the results of the ESS data. The cardiovascular outcome data were collected by a dedicated research assistant via telephone calls or clinic chart reviews, and all of the information was entered prospectively. Adverse cardiovascular events were defined as cardiac death, myocardial infarction, stroke, unplanned revascularization, or heart failure requiring hospitalization. To verify the events, source documents of the patients who had experienced adverse cardiovascular events were reviewed by the investigators.
We summarized the distribution of the continuous normally distributed clinical and laboratory procedural characteristics of the patients using the mean and standard deviation. The differences in the means of the sleepier and less sleepy groups were compared using an independent sample t test. For skewed continuous variables, the median and interquartile ranges were used to summarize the distribution, with comparisons between groups made with the Mann-Whitney test. For categorical variables, the Fisher exact test was used to compare differences in proportions.
For the analysis of time-to-adverse events, each participant's survival time was calculated from the date of index admission to the date when an adverse event first occurred. Patients who did not have an adverse event were censored on February 15, 2013. The Kaplan-Meier cumulative incidence curves were plotted and the difference in cumulative incidence of adverse event rates between the sleepier and less sleepy groups was compared using the log rank test. The Cox proportional hazards regression was then applied to adjust for body mass index and smoking in the time-to-adverse-event analysis. All of the statistical analyses were carried out using STATA version 10.0 (StataCorp LP, College Station, TX, USA), assuming a two-sided test with a 5% level of significance.
Among the 118 recruited patients, 117 completed the ESS and formed the study population. The distribution of the ESS scores is shown in Figure 2. The median ESS score was 8 (interquartile range 5-11). The baseline demographic and clinical characteristics of the sleepier (ESS > 10, n = 30) and less sleepy (ESS ≤ 10, n = 87) groups are shown in Table 1. The majority of the study patients were male. About 30% of the recruited patients had diabetes mellitus, but none had undergone previous coronary artery bypass grafting. The most common clinical presentations were ST-elevation myocardial infarction (n = 45) and non-ST-elevation myocardial infarction (n = 38). Compared with the less sleepy group, the sleepier group had higher serum levels of total and low-density-lipoprotein cholesterols. There were no significant differences between the sleepier and less sleepy groups with respect to full blood count, renal biochemistry, peak creatine kinase levels (for patients with acute myocardial infarction), or glycosylated hemoglobin levels (for patients with diabetes mellitus) (data not shown).
Distribution of Epworth Sleepiness Scale score
Patient demographics and clinical characteristics
There were no significant differences between the sleepier and less sleepy groups in the angiographic complexity of their coronary artery disease. Likewise, the incidence of multivessel coronary artery disease, location of culprit lesions, and left ventricular ejection fraction were similar between the 2 groups. The incidence of treatment for coronary artery disease using drug-eluting stents was similar between the sleepier and less sleepy groups. The IVUS findings are shown in Table 2. The culprit lesions were longer and had more fibrofatty tissues in the sleepier than in the less sleepy group. Slightly more than half of the culprit lesions were thin-cap fibroatheroma, with no difference in lesion type between the sleepier and less sleepy groups (data not shown).
Intravascular ultrasound findings
The median follow-up duration was 16 months (95% CI: 14.4-17.6). Complete data on follow-up were available for all 117 patients. Among the 30 patients in the sleepier group, 9 patients developed 10 adverse cardiovascular events. These included 2 cardiac deaths, 2 myocardial infarctions, 4 target vessel revascularizations, 1 stroke, and 1 heart failure admission. Among the 87 patients in the less sleepy group, 2 patients developed 4 adverse cardiovascular events. These included 2 myocardial infarctions and 2 target vessel revascularizations. The Kaplan-Meier cumulative incidence of adverse cardiovascular events is shown in Figure 3. The event rate at 16 months was higher in the sleepier than the less sleepy group (12.5% versus 6.9%, p = 0.03). The Cox regression analysis adjusting for age and smoking showed increased hazard of adverse event in sleepier group as compared to less sleepy group (HR = 3.44, 95% CI 1.01-11.72).
Kaplan-Meier cumulative incidence curves
We report the relationships between excessive daytime sleepiness, coronary plaque phenotype, and incidence of subsequent adverse cardiovascular events in a cohort of patients presenting with symptomatic coronary artery disease. A total of 117 patients underwent an IVUS interrogation of coronary stenosis and answered the ESS questionnaire during the same hospital admission. All of the recruited patients were treated according to standard clinical practice. The patients were classified into sleepier and less sleepy groups according to their baseline ESS scores (> 10 versus ≤ 10), and we found that the sleepier group was associated with longer lesion lengths. After adjusting for potential confounders, the hazard of adverse cardiovascular events was 3-fold in the sleepier as compared to the less sleepy groups.
The evaluation of excessive daytime sleepiness is often performed in the diagnosis of obstructive sleep apnea. In the general population, the association between excessive daytime sleepiness and obstructive sleep apnea has been clearly demonstrated. However, in patients with cardiovascular disorders, this association has proven to be weak.14–16 A possible factor that could explain in this discrepancy is the presence of "transient" obstructive sleep apnea in patients presenting with acute cardiovascular conditions. In addition, myocardial ischemia or heart failure alone can lead to fatigue and excessive daytime sleepiness, even in the absence of obstructive sleep apnea.17,18 Cardiac medications such as β-blockers can also lead to excessive daytime sleepiness. As a result of these entangled relationships, the true prognostic implication of excessive daytime sleepiness in patients presenting with cardiovascular disease has been inadvertently neglected.
Excessive daytime sleepiness is among the most frequent sleep complaints in the general population, yet the data on the effects of excessive daytime sleepiness on subsequent cardiovascular outcomes are limited. In the 1990s, the Cardiovascular Health Study reported that excessive daytime sleep was associated with subsequent cardiovascular mortality in otherwise healthy elderly women.6 A recent French study of over 7,000 healthy community-dwelling elderly subjects found that frequent excessive daytime sleepiness was independently associated with future vascular events, stroke, and cardiovascular mortality.4,5 However, in the aforementioned studies, objective tools such as ESS were not used, and subjects with pre-existing cardiovascular disorders were excluded.4–6 The aim of this study was thus to extend these results by exploring the association between baseline excessive daytime sleepiness and subsequent cardiovascular outcomes in patients presenting with coronary artery disease. We hypothesized that excessive daytime sleepiness is associated with complex coronary plaque phenotype and future adverse cardiovascular events.
Based on a median ESS scores (> 10 versus ≤ 10), we divided the patients into sleepier and less sleepy groups. The incidence of adverse cardiovascular events in the sleepier group was significantly higher than in the less sleepy group in our cohort of middle-aged (mean age 54) and predominantly male patients (88%), even after adjustment for potential confounding factors. The exact mechanisms for this association remain incompletely understood, but heightened sympathetic drive and elevated levels of circulating catecholamines, oxidative stress, endothelial dysfunction, and systemic inflammation have been reported as possible mechanisms.19–22 Our findings corroborate those of previous studies on healthy elderly people. If our observations are verified in larger-scale studies, then conducting the ESS questionnaire could be a simple and inexpensive tool to risk-stratify patients presenting with symptomatic coronary artery disease.
One of the strengths of this study is its use of IVUS rather than coronary angiography to assess the coronary plaque phenotype. As an intrinsic attempt to preserve the lumen and perfusion, the coronary arteries often develop outward remodeling in response to accumulations of atherosclerotic plaques. Thus, the early phase of coronary atherosclerosis is often undetectable by conventional coronary angiography, which depicts the lumen but not the vessel wall. In contrast, IVUS is an intra-coronary imaging technique that provides a three-dimensional tomographic view, and is superior to conventional coronary angiography in the assessment of coronary plaque phenotype.23
This study included patients with relatively severe forms of coronary artery disease, as is evidenced by the high proportion of patients with diabetes mellitus (30%), previous myocardial infarction (19%), and previous percutaneous coronary intervention (21%). In addition, 70% of the patients presented with acute myocardial infarction (ST- or non-ST- elevation myocardial infarction). Rather than resulting from selection bias, this pattern represents the current trend in the management of coronary artery disease. Recent data have suggested that in patients with stable angina, routine invasive management with angiography and percutaneous coronary intervention does not provide any incremental benefit compared with medical therapy alone.24 Thus, in recent years there have been fewer patients with stable angina undergoing coronary angiography, and acute myocardial infarction represents the most common indication of coronary angiography in our institutions.
This study has several limitations. This is a preliminary and hypothesis generating study due to the relatively small study size. The ESS scores were based on the patients' own responses, which were not validated by other family members. However, the number of family members differed among the patients, and the responses given by different family members may vary, which would make such validation unreliable. Also, Singapore is a multiethnic country, and its population includes Chinese, Malays, and Indians. The ESS was administered in English, and although English is the common language among people living in Singapore, it is not the mother tongue for many of them. The levels of language proficiency may have influenced the participants' understanding and interpretation of the ESS questionnaire. Further, the physicians conducting the outpatient clinic visits were blinded to the ESS data, but had access to the IVUS images. Although IVUS is a highly specialized interventional field that most outpatient physicians do not refer to, we could not exclude the possibility that some outpatient physicians may have modified their treatment after reviewing the IVUS images, and that such shifts in treatment may have ultimately changed the natural history of the patients' conditions. Finally, all of the patients in this study underwent clinically indicated coronary angiography, because angiography is a prerequisite for IVUS examinations. Thus, it may not be possible to extrapolate the results of this study to patients who are treated in more conservative ways.
In conclusion, we found that excessive daytime sleepiness (ESS > 10) was associated with longer lesion length in patients presenting symptomatic coronary artery disease. As of the completion of a 16-month follow-up period, the sleepier group was associated with significantly more adverse cardiovascular events than the less sleepy group. In the future, large-scale studies are warrented that target the association between the ESS and a diagnosis of obstuctive sleep apnea, and the effects of coronary artery disease treatment on the degree of excessive daytime sleepiness.
This was not an industry supported study. This study was funded by the Academic Research Fund (grant number R172-000-239-112) of the Ministry of Education, Singapore. The authors have indicated no financial conflicts of interest.
The authors gratefully acknowledge the assistance of Miss Pei-Ee Lee and Miss Venesa Loh with the recruitment of patients.
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text:
Methods for the estimation of incremental cost effectiveness
Search Medline for
|September 8, 2005
Introduction and Purpose
Meanwhile therapeutic and diagnostic procedures are not only evaluated from a clinical, but also from a health economic point of view to link their clinical efficacy to the underlying direct costs. Discussions on ressource allocation and the founding of medical supplementation can be based on the results of such cost effectiveness evaluations and therefore provide an objective rationale for decisions.
The estimation of incremental cost effectiveness ratios (ICERs) has earnt increasing attention during this decade. ICERs relate the cost difference between therapeutical alternatives to the corresponding difference in clinical efficacy or utility. Despite the intuitive interpretation of ICERs as additional costs per additional benefit unit, their statistical treatment imposes severe problems because of the necessity to estimate the distribution of a ratio of at least two stochastically dependent distributions [Ref. 1]. Several attempts were made to modify the well-known Fieller theorem for this purpose, other authors suggest the use of multivariate Bootstrap simulation or Bayesian approaches [Ref. 1], [Ref. 2] . Nevertheless, the problems in ratio estimation remain. Therefore, the concept of ICER estimation is contrasted to the idea of net health benefit (NHB) estimation, which transforms the former ratio estimation problem into a linear estimation procedure [Ref. 2].
Material and Methods
Model parametrization
The following will consider two therapeutic alternatives 1 and 2, where treatment 1 denotes an established standard procedure and treatment 2 is under discussion concerning possible recommendation for founding by health care insurers. If then the random variables K1 and K2 denote the treatments' costs and the corresponding random variables E1 and E2 the treatments' respective efficacies, the following will assume K2 > K1 and E2 > E1 (such a treatment alternative 2 is usually called "admissable" for ressource allocation). A cost effectiveness comparison of these treatments may then provide a decision on when to found treatment 2 instead of treatment 1, or when to retain ressource allocation to the standard treatment 1.
The ratio K / E is refered to as the cost effectiveness ratio (CER) and describes a treatment's marginal costs per gained clinical benefit unit. The incremental cost effectiveness ratio (ICER) of a treatment 2 versus the standard treatment 1 is defined as ICER21 = (K2 – K1) / (E2 – E1) and estimates the additional costs, which must be invested to achieve one additional clinical benefit unit under treatment 2 instead of the standard. In this sense, the ICER concept allows for "health economical ranking" of different health care service offers, when being contrasted to the same standard. Ressource allocation rules can now be formulated straigt-forward: If a health care insurer considers treatment 2 for founding, an allocation rule based on the ICER could use a pre-specified benchmark µ, which characterizes the insurer's maximum willingness to pay (WTP) additional treatment costs per gained benefit unit. Therefore treatment 2 would be founded as soon as µ > ICER21, whereas treatment 1 remains founded for CER1 < µ < ICER21.
A different concept for cost effectiveness evaluation is based on net health benefit estimation [3]: The net health benefit (NHB) of a treatment is defined as its clinical benefit after correction for its incremental costs when being contrasted to a standard, NHB = E – K/µ, where µ denotes the above willingness to pay benchmark. Therefore the net health benefit approach directly involves the WTP model parameter into cost effectiveness estimation. In this context the NHB measures a health service's benefit after correction for the insurer's willingness to pay philosophy. A new treatment alternative's incremental net health benefit versus a standard is then defined as INHB21 = NHB2 – NHB1 and measures the additional clinical benefit of treatment 2 after correction for the two treatment alternatives' relative cost effectiveness. An NHB-based allocation rule suggests founding of treatment 2 as soon as INHB21 > 0 (thereby NHB2 > NHB1) and founding of treatment 1 otherwise. It is easy to show, that the ICER-based and the INHB-based allocation rules yield the same allocation decisions [Ref. 3].
The cost and benefit parameters Ki and Ei can be estimated by their population means and imputed into the above allocation rules as follows:
- 1.
- Determine the WTP benchmark µ > 0 and a significance level α > 0.
- 2.
- Estimate the sample cost and efficacy estimates K and E and compute the NHB-estimates in terms of K and E via NHB = E – K/µ for both therapies.
- 3.
- Compute the incremental net health benefit INHB = NHB2 – NHB1 of treatment 2 versus the standard treatment 1.
- 4.
- Obtain a one-sided (1-α/2) confidence interval for INHB based on the appropriate t-distribution, or perform a one-sided t-test to ensure INHB>0.
Cataract Surgery Data
The above will be illustrated by means of the cost effectiveness evaluation of cataract surgery with multifocal intraocular lenses [Ref. 3]. One drawback of monofocal intraocular lenses consists in the frequent ongoing need for seeing aids after surgery, for example when reading or driving. Multifocal lenses often overcome this need; an increase in subjective quality of life can be expected. German health care insurers reimburse the costs of monofocal lens supplementation. However, founding of multifocal cataract surgery is still under discussion. To assess the incremental cost effectiveness of multifocal lens supplementation with respect to its putative quality of life benefit, data of a randomized trial in cataract patients have been re-analysed from a health economic point of view. Quality of life was assessed by means of a questionnaire-based utility value ranging from 0.0 to 1.0. A total of 400 patients were equally assigned to monofocal or multifocal lens supplementation, and a 6 months follow up on complications and post surgical quality of life was performed. The WTP benchmark was pre-specified at 800 € per gained QALY.
A remarkable difference in both costs and gained QALYs was found, whereas already the marginal cost effectiveness of supplementation with multifocal lenses (852 € per gained QALY) turned out worse than the corresponding monofocal estimate of 786 € per gained QALY. If only applied to mean point estimates, the ICER-based allocation rule would still decide founding of monofocal intraocular lenses, but no longer consider multifocal supplementation: ICER = 1060 € / QALY > 800 € / QALY = µ. The INHB-based allocation rule would yield the same decision: INHB = NHB(multifocal) – NHB(monofocal) = -0.133 QALYs – 0.028 QALYs = -0.161 QALYs < 0, i.e. multifocal cataract surgery results in a (slight) loss in cost effectiveness when contrasted to the monofocal therapeutic standard.
If the strategy in Section 2.2 is applied at a 5% significance level, a p-value of 0.045 (one-sided two sample t-test) results. Since p>0.025, no statistically significant difference in net health benefits was found between the multifocal and monofocal lens supplementation, where benefit was based on the number of QALYs achieved by the respective treatment. Therefore supplementation of cataract patients with multifocal intraocular lenses cannot be ensured to show a significantly positive net health benefit when compared to the monofocal supplementation standard.
Whereas the ICER-based approach provides somewhat instructive information, its statistical feasibility has to be based on severe model assumptions. The NHB approach, however, transforms the problem into standard linear estimation. In this context it is overly important, that the allocation rules based on the net health benefit approach yield the same allocation decisions as the ICER-based ones, since interval estimation in the NHB context can be reduced to standard univariate significance testing and interval estimation. Therefore the rather difficult interpretation of (I)NHB estimates becomes weakened by their advantages concerning statistical feasibility. On the other hand, communication of NHB estimates should be handled with care: Note, that the NHB point estimates in the cataract surgery example do not even slightly mirror the order of the underlying willingness to pay parameter µ! This motivates the integration of methodologists into both the planning and evaluation phase of cost effectiveness investigations [Ref. 4].
- 1.
- Wakker P, Klaassen MP. Confidence intervals for cost-effectiveness ratios. Health Economy 1995; 4: 373-81
- 2.
- Heitjan DF. Fieller's method and net health benefits. Health Economy 2000; 9: 327-35
- 3.
- Krummenauer F, Landwehr I. Incremental cost effectiveness evaluation in clinical research. European Journal of Medical Research 2005; 10: 18 - 23
- 4.
- Seither C. Vorschläge zur gesundheitsökonomischen Evaluation zahnärztlicher Präventionsprogramme im Kindesalter. Dissertation zur Erlangung des Grades "Dr. med. dent.", Fachbereich Medizin der Universität Mainz; 2004
- 5.
- Laska EM, Meissner M, Siegel C, Wanderling J. Statistical cost effectiveness analysis of two treatments based on net health benefits. Stat Med 2001; 20: 1279-1302

subset: commoncrawl


text:
Feb. 8, 2007
For the 2007 Lipscomb Bisons things have changed. With the loss of much of their 2006 starting lineup the Bisons will be forced to look toward their new recruits, many of which are freshman eagerly anticipating their first glimpse of NCAA Division I baseball.
In addition, Jeff Forehand will take over as head coach for the Bisons. The coaching staff will be rounded out with Brian Ryman being named the new assistant coach, and Lantz Wheeler returning as the pitching coach.
Returning as the starting catcher for the Bisons will be sophomore, Caleb Joseph. Last season Joseph batted .265 with 35 hits and 22 RBIs in 45 games.
"Caleb is coming off a really good year and we anticipate him carrying the bulk of the load behind the plate," Forehand said.
Sophomore Andrew Kincaid and freshman AJ Thomas are also expected to see some playing time in the catcher's role.
"When we went through fall practice everybody made significant strides as far as who would occupy most of the time behind the plate," Forehand said. "But if we had to start tomorrow, Caleb would probably catch the majority of the innings with the others running close seconds."
The first base position will be one decided by pitching match-ups with right-handed hitter Jared Pichiottino and left-handed hitter Justin Sanders likely receiving the majority of the playing time. Freshman Ryan Wilkins is also expected to play a large role at first.
"Fortunately Jared is a right-handed hitter and Justin is a left-handed hitter which will give us a lot of options as we match up against different pitchers," Forehand said. "Also Ryan Wilkins has really been making some significant strides towards playing time at first base.
"With all three of those guys, whoever does not occupy the first base option will have great opportunity to fill in for us at the designated hitter's role and also as a pinch hitter."
The Bisons will begin the season with four options at second base; Clay Lehning, Kevin Nelson, Andrew Nickerson, and Kevin Gavigan.
"They are all the same type player and they all have the same type build," Forehand said. "All of them have their quality that I feel like will be able to give us a dimension at second base, and all of them have a skill that they can do better than the others. So we will have to see how that shapes out at second base."
At shortstop, junior transfer Ben Williams is expected to receive the majority of the starts.
"He is a good runner, good hitter, and a good defender," Forehand said. "We anticipate him being a big part of our middle infield."
In addition, sophomore Branden Cadavid will likely see some time at shortstop. Last season Cadavid batted .309 with 17 hits and 10 RBIs in 23 games.
"Branden might be considered our best infielder and best defender overall," Forehand said.
At third base, in addition to Cadavid, freshman Donnie Amos will be relied on heavily.
"Donnie came in as a very good high school player," Forehand said. "He will probably spend some time in left field as well. He is a very good hitter so if third or left is not an option, he could also see some time as the designated hitter."
Left field is another position which could be determined by pitching match-ups. Eric Abend, a right-handed hitter, and Allen Bolden, a left-handed hitter, are expected to see the majority of the playing time.
In centerfield, senior transfer Casey Bond is expected to receive most of the starts.
"He will be a big part of our lineup and probably stabilize centerfield for us," Forehand said.
Junior transfer, Shane Simpkins is expected to receive a great deal of the playing time in right field. The Bisons also expect Simpkins to be a big offensive force for the team this season as well.
Michael Fahs, Dallas Crouch, Tyler Courson, and Cody Morris will also see some playing time in the outfield for the Bisons this season.
On the mound, Matt Schnelly will once again be looked towards to lead a young staff. Schnelly, a senior right-hander, led the team in innings pitched (96) and strikeouts (91) last season. Schnelly was also second on the team in ERA (4.88) and opposing batting average (.276). After pitching a complete game shut-out against a talented Pittsburgh lineup last season, Schnelly became the Bisons first player ever to be named Atlantic Sun Pitcher of the Week.
"Matt is going to anchor our pitching staff," Forehand said. "He was a big part of the team last year and he only continues to get better. We look for him to chew up a lot of innings for us on the weekend."
In addition to Schnelly, junior Paul Piennette will likely return as a conference starter this season.
"Paul made some quality starts last year and I look forward to him doing the same thing this year," Forehand said.
The final conference starter is expected to be senior transfer John King. King is a 6'3" right-hander from Peachtree City, Georgia.
Several pitchers are expected to see time as a mid-week starter, with senior Rob Smithson being one of them. In 17 appearances last season, Smithson was 4-2 with a 6.85 ERA.
"Smithson is another senior that can add some experience," Forehand said. "We don't know what his role will be as we start the season, but he will either be a starter or reliever for us and can add some experience and depth."
Despite such a large pitching staff, every pitcher is expected to be relied heavily upon in some capacity over the season. With such a large group of freshman pitchers, the success of the Bisons bullpen will reflect in large part the ability of the younger and less experienced freshman to handle the pressure.
Freshman pitchers include right-handers Matt Bowling, Taylor Merry and Dylan Ray, and left-hander Rex Brothers. Sophomores Josh Spicer, Jerry Young, Mike Zenko, Charles Williams, and Brandon McClurg will be joined by upper-classmen Chris Burnett, Sean Szymanski, and James Ogden.
The closer's role is expected to look much like it did last year, with sophomores Williams and McClurg likely to play a large role.
"McClurg and Williams will be a huge part of our bullpen," Forehand said. "Both of those guys are solid, solid pitchers coming out of the bullpen for us and can provide some quality innings for us."
The Lipscomb baseball scene has certainly changed. Equipped with a new coach, numerous pitching recruits, and a drastically altered lineup the Bisons are confident that their place in the conference standings will improve also.
By Krissy Wade


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I have drove hondas before this is the worst. I am spending more money on repairs than the value of the car. I think I am going to try a camary next. I had issues with the front axles, airbags and the car was not in ANY accidents!! Even Honda couldnt understand it, which I think was a LIE!
2004 Honda Accord Ratings, Reviews and Analysis
As the model was fully redesigned for the 2003 model year, there are only a few changes on the 2004 Honda Accord. Availability of side curtain airbags has been expanded this year to four-cylinder EX models -- standard on those with leather, optional on cars with a cloth interior. All four- and six-cylinder EX models equipped with a leather interior now have XM Satellite Radio with three months of free service as standard equipment. And as with all Honda cars this year, a new seatbelt reminder system is standard. Accord models meeting California's stringent Partial Zero Emissions Vehicle (PZEV) standards -- all four-cylinder sedans equipped with automatic transmission -- will also be sold in the states of New York, Maine, Vermont and Massachusetts.
Ratings & Reviews
I have owned this car since new. And the paint/clear coat has deteriorated down to bare metal along much of the top surfaces of the car and is showing signs of surface rust. I have taken this issue to Honda's Regional Manager and they are refusing to even pay for part of the repair, let alone all of it. So now I have to decide if I want to spend $4500 (the cost of a new engine, or 10 timing belts) on a car that's worth over $10,500 (with good paint) or not. This is my 6th Honda and may very well be my last, as I am not buying from a Manufacturer that skimps on their paint and clear coat. This problem has been expressed by 100's and possibly 1000's of Honda owners around the world.
I have owned many cars including 4 Hondas, and this is the most reliable, lowest cost to own of them all. Tons of room for our family of 4 and only routine maintenance so far (oil, brakes, tires, etc.). Could get a little better mpg for a 4 cyl car, but gets over 30 mpg on the highway so can't complain too much. Very comfortable leather interior, good legroom (I'm 6'5" tall), and plenty of trunk space. Car now has 132,000 miles and doesn't leak or burn any oil, and the transmission still feels very strong with no issues so far. Can't imagine being happier with another car. Have always liked Hondas, but this one is by far the best I've owned.
Read these reviews and you see Honda is not the reliability car we were lead to believe. I purchased this money pit new because I drive for work and wanted a car that would last and not nickel and dime me down the road. Wow did I pick the wrong car! The transmission had a recall and I took it in at 18K. They checked it out and install a oil kit. At 48k dropped out and Honda would not cover the labor of $700. They did replace the radio that failed around the same time. Since then the power steering motor, master cylinder, radiator and struts all have failed and needed replacing for a total of over $2,500 not including the transmission. NEVER BUY A HONDA!
Purchased this car in April 09' with just under 28k. Now at 58K and no problems. Great performance from the V6.Fuel economy is excellent at 28 - 32 mpg. I do my own maintenance which includes draining and filing the transmission fluid every 15k. "Honda Trans fluid only.


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Home > Who We Are > News > St. Vincent's Sponsors New downtown exercise initiative in Jacksonville
Published on March 06, 2013
There is a new initiative in Jacksonville that hopes to bring more fitness to the downtown area.
"I'm a downtown resident. I'm a Jacksonville native," said program creator Donteacia Seymore. "I've been here when downtown was bubbling, and I am here now. I kind of wanna see it come back to, you know, the way it used to be in the early 80s and 90s."
Bringing downtown back to what it once was is one of the main reasons Seymore says Fitness in the Plaza was created.
"Fitness in the Plaza is an opportunity for Jacksonville residents to come downtown, experience our beautiful landscape and get a good workout at the same time," said Seymore.
Fitness in the Plaza isn't just for adults, it's also designed to get kids moving.
"We know that about a third of children in our area are overweight, and 70 percent of them will grow up to be overweight, so we want to change that practice," said St. Vincent's CEO Moody Chilsolm.
According to the Centers for Disease Control, more than 35 percent of people in Jacksonville are considered overweight, 26 percent of them are categorized as obese and nearly 28 percent say they do no physical activity at all.
"These events will give people a great opportunity to come out and participate in something that doesn't cost them anything," said Chilsolm. "Whether it's Zumba or whether it's senior silver sneakers classes or children activity programs."
If you are interested in participating in Fitness in the Plaza head to fitnessintheplaza.com for more information.
View the article.
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Economics is easy to understand. Wealth comes from human beings. It's as simple as that. It comes from human beings engaging with nature in an intelligent and productive way in order to make all of the things we want and need. It is work that makes wealth.
Read more here: http://hubpages.com/hub/We-do-the-work-Someone-else-takes-the-wealth
Saturday, August 21, 2010
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Danger (From The Love Of Ray J) Admits She Was A Prostitute & Is Engaged To Nick Cannon's Brother!
Danger from "The Love Of Ray J" clears up rumors with Tiffani Webb. the host and creator of Girl Talk NYC.
Please click the "Report" button below if the video on this page is not working properly.
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Winner gets the above shown DVD signed on the cover by LISA ANN! A picture of LISA ANN taken during one of our signings will be included!
S&H is $5 USA and $10 international. use BUY IT NOW for FREE S&H! Winner will get an invoice shortly after the listing ends and will then have 48 hrs to make payment. Thanks!


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Express. Home of the Daily and Sunday Express.
No discussions over Laudrup future
Swansea chairman Huw Jenkins has dismissed suggestions Michael Laudrup's future as manager has been discussed.
Speculation surfaced following Saturday's 2-0 loss at West Ham that Laudrup's tenure as boss could come to an end as Swansea fight for their Premier League status.
"I haven't heard anything in reference to Michael and neither have we met, or discussed, or done anything about Michael," Jenkins told BBC Sport Wales.
"A couple of us did actually meet up on Sunday morning to have a cup of coffee like we normally do. That's as simple as it was. That's where the first rumour came from.
"It's difficult for me to say anything because there isn't anything to discuss.
"When you end up losing matches, when everything is so tight at the bottom of the Premier League, you get rumours and you get stories. We have had them for many weeks.
"If we win everything is fine. If we lose it's not."
The Upton Park defeat left the Swans with one win from 10 Premier League games ahead of Saturday's south Wales derby at home to Cardiff.
Swansea are 12th in a congested table, two points above the Hammers, who occupy the final place in the relegation zone, three points clear of 19th-placed Cardiff and five points better off than bottom club Fulham.
Jenkins added: "The bigger picture as always is winning a Premier League match and it so happens this week we are playing Cardiff.
"Winning the match, I can assure you, is the most important thing for both teams."


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Chocolate Dipped Cookies {bite sized}
I wanted to let you all know my little old food blog known as Shugary Sweets turned one years old this month. I began blogging many years before, just to share pictures and stories with family and friends. Then in January of last year I began sharing recipes. In May of 2011, I purchased my domain name and officially began food blogging on a regular basis on my new blog, Shugary Sweets.
Over the last few days I've posed this silly question to all of you…and I received some funny responses. Here are some of your answers, plus a few of my own…
"You Might Be a Food Blogger If…."
…the dust in your kitchen is actually flour (or powdered sugar in my case)
…your children often ask if the treat has been photographed or can they eat it yet
…dinner is cold because you were trying to get the right picture
…you plan vacations around food stops (Carlo's Bakery??)
…you spend more time "talking" to online blog friends than you do your neighbors
…you buy cute straws, to use at props not for drinking out of
…you skip past an entire post just to get to the giveaway (hello?? anyone there???)
Now for the recipe. I made these sweet little chocolate chip cookies bite sized. Okay, two bite. Then, I went one more step and dunked their little bottoms in chocolate. Because why not? And if you don't want 11 dozen cookies, you can easily cut this recipe down…or freeze them!
Chocolate Dipped Cookies
- 1½ cup Crisco (butter flavored)
- 2½ cup brown sugar
- ¼ cup milk
- 2 Tbsp vanilla extract
- 2 egg
- 3½ cup flour
- 2 tsp salt
- 1½ tsp baking soda
- 2 pinches of nutmeg
- 1 tsp cinnamon
- 18 oz milk chocolate morsels
- 24 oz chocolate candy bark, for dipping
- Combine crisco, sugar, milk and vanilla. Beat in eggs. Add dry ingredients and combine thoroughly. Add in morsels.
- To make these bite sized, I used a small one tablespoon scoop.
- Bake in a 375 degree oven for 8-11 minutes, until lightly browned on top. Of course, I recommend using a stone to cook these on, to get even browning.
- Cool completely. Melt chocolate bark according to package directions. Dip bottoms of cookies in chocolate and lay (chocolate side down) directly on parchment paper. Allow to set (about 15 minutes). Store covered.
**There may be affiliate links in this post! By clicking on them, or purchasing recommended items I may receive a small compensation. However, I only recommend products I love! Thank you for supporting Shugary Sweets! See my disclosure policy for more info**


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PTC's end-to-end dynamic publishing solution streamlines how organizations create, manage and publish technical information.
In today's global marketplace—where businesses are operating across borders and time zones—your customers demand that accurate, relevant product information be delivered in real-time. Arbortext provides the capability to define, author, illustrate, manage and deliver dynamic product information—in the user's preferred language and format—on demand.
Through PTC Service Lifecycle Management (SLM) software solutions that can be deployed either collectively or in parallel, Arbortext helps you overcome the challenges of your traditional, outdated product documentation practices.


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Holland Bar Stools - 63018BWNatOakBAxsPap - 630 Voltaire Chair With Natural Oak B Back
Originally $222.00 - Save 37%
Price: $140.00
Questions about Holland Bar Stools - 63018BWNatOakBAxsPap
The plumbing professionals at Great Northern Kitchen and Bath are available to assist you with your selection of Holland Bar Stools products.
Email an Expert or call 888-844-0012
Holland Bar Stools - 63018BWNatOakBAxsPap
Customize Your Very Own Chair With The Help Of Holland Bar Stool Co.! This Voltaire Chair Has A Contemporary Design And Provides Superb Back Support. The Frame Is Made From Commercial Quality Steel That Is Strong And Durable, And Is Powder-Coated To Ensure A Long-Lasting, Rich Finish. Elegant Wood Back Is Oak With A Natural Finish. Our Wood Seats Are Made Of 1 1/4 Inch Hardwood That Are Dished For Comfort. Our Cushion Seats Are Of The Highest Quality As Well, Utilizing A Breathable, Commercial Grade Vinyl Or Fabric. Underneath This Is 2 1/2 Inches Of Highly-Dense Foam To Provide Maximum Support. The Framework Itself Is Very Sturdy, Using Only Solid Mig Welds Ensuring The Integrity Of The Structure. You Can'T Find A Higher Quality Stool On The Market. If You Are Going To Finish Your Bar Or Dining Area - Do It Right, With A Holland Bar Stool.
|Online Product ID:
|Black Wrinkle
|Made in USA:
|22 lbs.
|Product Type:
|Steel Frame
|5 Year Residential Structural Frame Warranty.
|L:19"x W:19"x H:33"
- Solid Welded Frame
- Finished With A Epoxy-Polyester Powder Coat, Providing A Durable, Long Lasting Finish
- Made With Commercial Quality, Plating Grade Steel
- Custom, Rounded Floor Glides Help Prevent Floor Scratching
- Maximum Weight Limit Is 350 Lbs
- Axis Paprika Seat
63018BWNatOakBAxsPap - Holland Bar Stools
Great Northern Kitchen and Bath is proud to present this decorative chair, by Holland Bar Stools. The 63018BWNatOakBAxsPap is made from premium materials, this Chair offers great function and value for your home. This fixture is part of Holland Bar Stools's decorative Collection, so make sure to check out other styles of fixtures to accessorize your room.
The Holland Bar Stool Company's logo "Kiss of Quality" stands for the pride we take in our products and services. It is a constant reminder that nothing but the best will do. From the raw parts to the finished product, our utmost attention is focused on detail to ensure that our products will be guaranteed to please the customer. Holland Bar Stool Company is based in Holland, Michigan, where we manufacture and ship our products. Our merchandise is constructed from the finest solid Red Appalachian Oak or solid hardwood maple for the wood products, and high quality plating grade steel for metal products. Our metal stools have an oven baked powdercoat finish that is extremely durable and long lasting, while our wood is finished with the finest catalyzed lacquer in the industry. We offer a variety of sizes: 18? chairs, 24? counter stools, 30? and 36? bar stools, a number of finishes for both wood and metal products, and a huge assortment of upholstery options. We offer custom heights, custom wood finishes, and since we have our own upholstery department C.O.M.'s are always welcome. We can also supply to you, free of charge, custom literature for your showroom. We make doing business with our company as easy as possible. Our average lead-time for QuickShip items is 7 days, and we have no minimum order! In essence, we are your inventory allowing you to save on valuable warehouse space and inventory investment. All of our products are normally shipped via Federal Express; we even drop ship directly to your customer if requested. Whether for residential or commercial use, we are sure to have something for all settings and applications. Our offerings are sure to please.
Holland Bar Stools Warranty


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Performance tools to keep you on your game...
Countdown to Your Race
- In the widget above, click on "Get & Share" bar with the blue asterix.
- Click on the Options icon - - on the Options bar.
- Enter your event name and date. Date should be in MM/DD/YYYY format.
- Click "Save" and then "Close".
You will see your newly entered event once you "Get & Share" the widget in the next step.
- Click on the "Get & Share" bar with the blue asterix and choose a service in which to embed your new, personalized countdown widget.
flash widget here


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News >> Browse Articles >> Job & Career Advice
How to Make a Great First Impression
Make yourself stand out with a great first impression every time!
Elizabeth Hoyt
February 06, 2017
Whether you're interviewing for a job, internship, scholarship, at a networking event or, even, meeting your significant other's parents for the first time, you want to make a great first impression.
It's understandable that you're nervous and sometimes your nerves can get the best of you.
Even if you're great at concealing your nerves, you want to come across as genuine rather than arrogant or rehearsed.
Here are some tips to follow that can help you make a great first impression in any given scenario:
Learn Names – the First Time Around (and Remember Them!)
This is definitely much easier said than done.
However, there are a few easy tricks you can utilize to remember someone's name when you first meet them. All tricks can be used in tandem to almost guarantee you'll become a name virtuoso in no time!
Trick #1: When introduced, say their name aloud. For example, "Hi, John. I'm Elizabeth. It's great to finally meet you after hearing so many wonderful things about your work in the field."
Trick #2: When you learn someone's name, associate the first letter of their name with an obscure object or animal. For example, let's assume you meet someone named Anne. You can associate Anne with Aardvarks. You're not likely to forget Anne Ardvarks and will likely remember her name as a result.
Trick #3: This involves recalling names. When trying to recall someone's name, run through the alphabet, starting with the letter "A." It's much easier if you go through the alphabet, letter by letter, thinking of names to pinpoint what a person's name is. You may be surprised what you can remember using this method!
Make Eye Contact
When you're speaking to someone, it's important to make eye contact to show that you're actively listening to what they're saying and understanding. If your eyes are darting around the room, it can appear as if you're nervous or uninterested.
Inversely, you don't want to stare at them the entire time. Maintain eye contact, looking away once in a while so that neither of you are uncomfortable or having a staring contest.
Master the Art of Shaking Hands
It's polite to shake hands at the beginning and end of a conversation. A quick, firm grasp of the hand is perfect – avoid limp noodle handshakes at all costs!
Those types of handshakes command little respect and give off the impression that you're neither excited nor fully present for the conversation that's about to take place.
Starting out with a great handshake says, "I'm ready for a great discussion," and ending with one sets the tone for a great future.
Pay Attention to Your Body Language
According to The Nonverbal Group, a whopping 93 percent of all daily communication is actually nonverbal! That means that only seven percent of what you're saying matters – everything else comes across through facial expressions and body language. That being said, you must pay attention to what you're saying with your body.
Here are a few body language dos and don'ts:
• Sit up straight/Stand tall – this displays confidence
• Move slowly – this displays composure
• Lean forward, slightly – this displays that you're engaged and interested in conversation
• Smile – a smile always conveys that you're enthusiastic and happy to be where you are
• Slouch – others perceive you as unconfident
• Touch your face/neck areas – others see you as uncertain, unsure of yourself
• Move hastily – others tend to feel nervous or uneasy
• Fold your arms – this tends to reflect that you're closed off to others
• Fidget – this tends to come across as nervous, which can makes others nervous as well
Look Interested
Eye contact, coupled with nonverbal cues can aid in looking interested while others are speaking to you. You always want to look interested in what others are saying – no matter how boring their topic of conversation may be.
Looking disinterested is not only rude but can give off an extremely bad impression. Obviously, they feel that whatever they are saying is worthwhile, otherwise they would not be saying it.
Give Nonverbal Cues
Similar to body language, it's important to give nonverbal cues while someone is speaking to indicate that they have your undivided attention. Examples include head nods, maintaining eye contact, laughing or smiling at their jokes or emotionally reacting properly otherwise to their stories.
Speak Clearly
When it's your turn to speak, you want to ensure that you're speaking clearly and not mumbling. A great way to tell if you're doing so is if others are repeatedly asking you to speak up or repeat yourself.
While speaking, it's important to vary your speech patterns to avoid dull or monotonous tones which can become very boring.
Change up the pace at different points, emphasize different words that are more important and take moments to pause whenever you need a break to either collect your thoughts or have a sip of water.
Dress to Impress
You don't need to dress as if you're a fashion icon, but it is important to look polished and put together. Aim to be presentable and wear clothes that are well fitting. Ensure that, in addition to your clothing, your hair, skin and nails are well groomed and hygienic as well.
Ultimately, the point is not to appear physically attractive – it is so that nothing is distracting from what you are trying to say.
Never underestimate the power of your smile! A smile can turn a bad situation upside down in an instant so always keep it in your back pocket. It's your best and most effective tool in any social situation.


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[Illinois] CMMB IGERT & M-CNTC Annual Symposium: Program Overview
Licensed according to this deed.
Published on
M Taher Saif PhD, Mechanical Engineering, Illinois
Professor Saif's research focuses on the mechanics of nanoscale materials and living cells. He uses both theory and experiment to explore (1) the effect of size on the mechanics of materials, and (2) the role of mechanical force in determining the functionality of cells and cell clusters.
Professor Saif demonstrated experimentally, for the first time, that plastic deformation in nanocrystalline metal films can be reversible. After plastic deformation, metals with grain sizes between 50 and 100 nanometers recover most of their plastic strain under macroscopically stress-free condition. This recovery is time dependent and thermally activated. Saif showed that the recovery originates from the small size and heterogeniety of microstructure of the metal specimens. The research, which was reported in Science, raises the possibility of manufacturing metal components that can heal themselves after being deformed or dented.
In the area of cellular mechanics, Professor Saif's projects involve neurons, cancer and cardiac cells, and interactions between cells in clusters. He seeks to address questions such as: What is the role of tension in neurons on memory and learning? Does mechanical microenvironment influence the onset of metastasis during cancer development? Can clusters of cells be guided so that they evolve into biological machines? He, together with Professor Akira Chiba of the the University of Maimi, showed that neurons are under mechanical tension, and that such tension might be essential for memory and learning.
Sponsored by
Midwest Cancer Nanotechnology Traning Center (M-CNTC) Training the next generation of leaders who will define the new frontiers and applications of nanotechnology in cancer research It is known that more than 1.5 million Americans were diagnosed with cancer during 2010, and half a million have died (Cancer Statistics 2010, ACS). In spite of considerable effort, there has been limited success in reducing per capita deaths from cancer since 1950. This calls for a paradigm shift in the understanding, detection, and intervention of the evolution of cancer from a single cell to tumor scale.
In response to this challenge the M-CNTC has assembled a preeminent interdisciplinary team of researchers and educators across the University of Illinois and clinical collaborators in the Midwest to train the next generation of engineers, physical scientists, and biologists to address the challenge of understanding, managing, diagnosing, and treating cancer using the most recent advancements in nanotechnology.
Cellular and Molecular Mechanics and Bionanotechnology (CMMB-IGERT) Training the next generation of leaders who will define the new frontiers of cellular and molecular mechanics and bionanotechnology Critical experiments during the last decade show a fundamental link between the micro- and macro-mechanical environment (i.e., intracellular forces, local shear, gravitational force) and a variety of cell functionalities, their lineage, and phenotype. These findings pose the grand challenge: what is the underlying molecular mechanism that cells employ to transduce mechanical signals to biochemical pathways?
In response to this challenge the CMMB IGERT launched an interdisciplinary research effort with national and international collaborators.
Cite this work
Researchers should cite this work as follows:
University of Illinois at Urbana-Champaign


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GMAT makes official releases to the public approximately once every 6-12 months.
Official Releases
GMAT is a cross-platform application, but we publish binaries on Windows only. For other platforms, see below to start from source. The latest official version is R2012a, released May 23, 2012.
- Windows installer (get this if you aren't sure)
- Windows zip file
- Source code and data (for developers)
- All Releases (SourceForge project page)
Certain plugins are disabled by default. These can be enabled by uncommenting the appropriate
PLUGIN lines in
libMatlabInterface(see Configuring the MATLAB Interface for configuration)
Source Code
If you use Mac or Linux, or if you just want the latest code, you can choose to build GMAT yourself. Our continuously-updated public code is hosted in the following Subversion repository:
See Development for compiling instructions.
Internal Users
Internal (NASA GSFC) users can download GMAT from the project's network share.
Internal Releases
We have special installers and binaries for internal users that contain some extra plugins we don't yet have permission to release. Browse to this location:
The following files are available:
gmat-internal-winInstaller-i586-R2012a-Beta.exe: Windows installer (internal version)
gmat-internal-win-i586-R2012a-Beta.zip: Windows zip distribution (internal version)
internalplugins.zip: extra plugins for the public releases. Extract this file over your existing GMAT installation to add the extra plugins, then uncomment the appropriate
PLUGINlines in
GMAT\bin\gmat_startup_file.txtto enable them.
Daily Builds
We post daily development builds to the following location:
This location contains these folders:
LatestCompleteVersion: the latest full GMAT instance. Copy this to your computer and run
YYYY-MM-DDfolders: compiled files only from that day's build. To use this, copy the contents over your existing GMAT installation. Note that if the two versions are very different, changes in other files may render your GMAT installation inoperable. If this happens, start with
LatestCompleteVersion, above.
Source Code
The main source code repository is the public SourceForge-hosted one above. Certain internal plugins and other unreleased files are stored in the following internal repository:
See the GMAT development team for access.


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LOS ANGELES — The walk-off hero, Ronnie Shaeffer, said he sneaked his game-winning single by UCLA first baseman Dean Espy in the bottom of the ninth inning to give the Anteaters a 4-3 win in the NCAA Los Angeles baseball regional Sunday at Jackie Robinson Stadium.
Some would say UCI (42-16) also sneaked by the top-seeded Bruins (35-24) without having to face their two best starting pitchers, Gerrit Cole and Trevor Bauer, to claim the program's third regional crown in five seasons.
Cole, selected No.1 in the major league draft by the Pittsburgh Pirates on Monday, and Bauer, the Collegiate Baseball Player of the Year who went No. 3 to the Arizona Diamondbacks, were deemed perhaps the two best pitchers in UCLA history by Bruins Coach and former UCI head man John Savage. But when San Francisco upset Cole in the opening round Friday, Bauer and the Bruins were relegated to outdueling Fresno State in Saturday's elimination round.
UCLA then burned No. 3 starter, Adam Plutko (who Savage called the best freshman pitcher in the country) in another elimination game Sunday morning against USF, leaving mid-week starter Zack Weiss, another freshman, to make his third start against UCI this season.
The Anteaters, who are 9-0 in winning the Round Rock (Texas), Lincoln (Neb.) and Los Angeles regionals in 2007, 2008 and 2011, respectively, will not however miss Virginia ace Danny Hultzen when they venture to Charlottesville, Va. for the best-of-three super regional that opens Saturday at 10 a.m. Sunday's game starts at 10 a.m. Both games will be aired on ESPNU.
If a third game is needed it will be Monday at 10 a.m., 1 p.m. or 4 p.m.
Hultzen, a junior left-hander picked No. 2 overall Monday by the Seattle Mariners, is 11-3 with a 1.57 earned-run average this season and is 31-5 with a 2.18 ERA and 378 strikeouts in 305 1/3 career innings.
Hultzen is also hitting .336 with one home run and 34 runs batted in this season. He was seven for 11 with five RBIs in three regional games, in which the Cavaliers (52-9), the No. 1 national seed, outscored their opponents, 29-3.
Hultzen pitched 7 1/3 shutout innings against the 'Eaters as a freshmen, when UVA defeated UCI twice to eliminate UCI from the 2009 Irvine Regional at Anteater Ballpark.
UCI is 1-1 in super regionals. It swept Wichita State in 2007 to earn the program's first and only trip to the College World Series. UCI was three outs away from sweeping at LSU in a 2008 super regional, before the Tigers rallied to win Game 2 and cruised to victory in the deciding third game. The 2008 regional had been the last dog-pile situation for UCI, until Sunday, when the 'Eaters used their ability to produce myriad heroes to end the Bruins' season.
Shaeffer, who had two hits in his last 28 regular-season at-bats, and struck out in his first regional at-bat to make it 10 Ks in 29 at-bats, got the biggest hit of the season with the aforementioned opposite-field single with two strikes and runners on second and third with no outs.
The hit, which would have been a two-run double had the game not officially ended when the run scored from third, made the first-team All-Big West catcher six for 10 in the regional with five RBIs to capture the four-team tournament's Most Outstanding Player award.
Senior pinch-hitter Jon Hurst opened the winning rally with a nine-pitch walk off Weiss, who was then lifted for reliever Nick Vander Tuig.
Junior designated hitter Jordan Leyland, whose six RBIs in the regional led all players, greeted Vander Tuig with an RBI double into the left-field corner.
Junior second baseman Tommy Reyes, who was six for 11 and scored four runs on his way to all-regional honors, followed with a bunt single down the third-base line to put runners at the corners. He then stole second to set the stage for Shaeffer.
"We had charts on these [UCLA pitchers] from the last two times we played them [a regular-season nonconference split with both teams winning at home] and they had thrown me a lot of fastballs in those two games," Shaeffer said. "That double in the fifth [an RBI blow that capped a two-run inning that cut into a 3-0 deficit] was an off-speed pitch, so I was sitting there ready for some fastballs."
Senior Brian Hernandez singled in the first UCI run and provided his usual sparkling defense at third base.
Junior first baseman Jordan Fox made two diving stops to rob would-be hits.
Nick Hoover, Andy Lines and Phil Ferragamo combined for 3 2/3 innings of one-hit, shutout relief to back up freshman starter Andrew Thurman, who allowed eight hits and three runs before exiting with one out in the sixth.
Ferragamo, a freshman who struck out the side in the ninth and left the bases loaded in the eighth, earned the win and is 2-0.
UCLA left 13 runners on base and stranded 40 in four tournament games.
Leyland, Reyes and Shaeffer, the bottom third of the batting order, had six of UCI's nine hits.
Junior shortstop D.J. Crumlich (five for 10 with two RBIs) and Hernandez (four for 13 with two RBIs) were also all-regional honorees for UCI, which Anteaters Coach Mike Gillespie said continues to the get the most out of its talent.
"It's a special achievement for us," said Gillespie, who has now guided 10 teams into at least the super regionals in 24 seasons, the first 20 at USC. "I really feel that these guys have played as close to their level of ability as any team I've had. A variety of different guys have come up big in different situations in different games."
Weiss, who earned one win and left his two other starts against UCI leading this season, gave the Anteaters credit.
"I think they're a very good team," said Weiss, who played at Northwood High in Irvine. "They do the little things right … They're scrappy and they are tough outs. There is not an easy out in that lineup."


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Cleats and Dignity
The civil rights struggle for African Americans happened in every sphere of life. Breaking the Line: The Season in Black College Football That Transformed the Sport and Changed the Course of Civil Rights, by Samuel G. Freedman, tells of two great black coaches in the tense year of 1967. Simon & Schuster
Catching Fire
One project of the USC Center for Religion and Civic Culture is the Pentecostal and Charismatic Research Initiative, which funded research in more than 20 countries. PCRI resources include the informative recent report, "Moved by the Spirit: Pentecostal and Charismatic Christianity in the Global South." crcc.usc.edu/pcri
Hope and Healing
The documentary film The Adventists 2 looks at health care in the developing world and Seventh-day Adventist medical missions in Haiti, the Amazon, Malawi, China, Peru, and the Dominican Republic. A sequel to the award-winning film The Adventists, which looked at the body-mind-spirit connections of Adventists. journeyfilms.com
A Light for the World
Get international and justice-minded perspectives on the Sunday scripture readings from Catholic sisters, priests, brothers, and lay missioners in A Maryknoll Liturgical Year: Reflections on the Readings for Year A, edited by Judy Coode and Kathy McNeely. Orbis


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The Nikita Chickita Snowdown will be a day long shred session, bringing the most progressive female snowboarders in the world together for a day of fun, style, and, of course, a chance to vie for their share of the $10,000 prize purse and one of 4 trips to the Icelandic Park Project in Iceland. Complete with live music, BBQ, friends and one hell-of-an after party, the Nikita Chickita Snowdown will be a day of snowboarding a la snowboarders who love to snowboard.
"We wanted to have a contest that highlights all of the things we love about snowboarding. For us this means riding with friends in an environment that is challenging, but most of all fun and with nothing cheesy or corporate involved, says Nikita's owner and designer Heida Birgisdottir. "We knew Northstar could put down the kind of course we were after, and when we teamed up with Ride Snowboards and Snowboarder Magazine we knew we were on the same page. We're really excited to be sharing this contest with them.
Ride Snowboards agrees. "We're thrilled to be presenting this event with Nikita, says Tara Miller, Marketing Manager for Ride. "With Priscilla Levac who was just named 'Rider of the Year' by Snowboarder and Janna Meyen who won 'Rider of the Year' at the Transworld Riders' Poll Awards leading the lady front for Ride, it's high time we give them and other female competitors their own event and recognition."
With a park designed by Northstar at Tahoe, the Nikita Chickita Snowdown will feature both Am and Pro Slopestyle and Rail Jam divisions, sending home the top-notch shredders with their portion of the $10,000 prize purse and 4 lucky ladies with a week-long trip to Iceland. Both divisions will be invite only, with the Pro riders responsible for choosing which Ams will compete.
"Having the Pros choose the Ams will really showcase where current Pros believe the future is headed, adds Birgisdottir. "We really want to have the best of both worlds involved with this. We want to show everyone how good the girls actually are, and we believe this format will not only spotlight the best girls in the world, but also the gals that aren't quite on the radar yet.
For more information on the Snowdown, please visit www.nikitaclothing.com.


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1/ While any goods for return are in your possession, you are obliged to take 'Reasonable Care' of them.
2/ All goods will remain your liability until safe receipt is acknowledged by Body Kit Limited.
3/ We can only accept the return of used or modified goods at our sole discretion.
4/ Where orders are cancelled and/or returned, we are not liable for your return shipping costs (unless we have supplied faulty or incorrect goods).
For your convenience, we can arrange home collections (Monday to Friday - not public holidays) or a range of local drop shop options, shown below. Those one off costs will be agreed with you in advance and will be deducted from your refund.
PLEASE NOTE: Couriers will normally only attempt collection once on the specified day, any further collection attempts will incur further charges.
Please do not return goods without authorization or via any service without tracking or proof of delivery, we may not be able to refund.
Return option 1. (small packets or parcels > 2kg)
For Small Packets/Parcels please use Royal Mail 1st Class Signed For Service (this can be added to the refund amount).
If you are not sure what your parcel/packet is, please refer to the Royal Mail Size Guide.
Return option 2.
Courier Collection: Monday to Friday 8am - 6pm (Not public holidays).
Note: A B/W printer is required and a departure signature is required (Label can also be posted).
For your convenience, as well as your home, collection can be from a different address, i.e. neighbour's house or work address (UK Mainland only).
Return option 3.
Post Office/MyHermes Drop off: Monday to Sunday (Local opening times vary).
We send you a Return Label by email (B/W Printer required) or by Surface Mail. Your goods for return can then be dropped at any UK Mainland Post Office or MyHermes Drop Shop.
Note: If we arrange a return collection with you and it fails because there is nobody in, the cost of any further collection attempts will be deducted from any refund due.
1. If a pre-arranged Home Collection or Post Office drop off fails because there was nobody home or the parcel was not dropped at the Post Office before the label expires, we will deduct the cost of any subsequent collection attempts from any refund, at the prevailing contracted rate.
2. Goods remain your liability until they are received by Body Kit Limited or it's Agent.
3. You are obliged to take reasonable care of those goods until we receive them and you must return our goods safely contained within their original or equivalent packaging.
4. Where goods have been **modified, painted, specially ordered or otherwise personalised / customised, we can normally accept them for return, at our discretion and reserve the right to right to raise handling or re-stocking fee of up to 50%.
5. Refunds
Where goods are returned under the provisions of the Consumer Contracts Regulations 2014 we are obliged to complete your refund within 14 days of safe receipt of any returned goods.
However, we will normally endeavour to complete refunds to most debit/credit cards in up to 5-10 Working Days and PayPal Accounts in up to 1-3 Working Days.
For security reasons, we can only issue refunds to the original payment source up to 30 days.
After 30 days, refunds can only be made via standard cheque or Bank transfer (Bank Account details are required).
6. Goods damaged in transit.
All orders are carefully inspected by trained staff before dispatch, but sometimes they can get damaged in transit.
On arrival, please inspect your goods carefully before signing for them, please tell your courier and then inform us of any damage within 24 hours of receipt, by phone or e-mail.
7. Faulty or incorrect goods.
Very occasionally and sometimes despite our best efforts, the wrong product might arrive or it may not fit your vehicle for some reason.
This is something we try hard to avoid but if a product proves to be faulty or incorrect, please contact us to arrange a replacement.
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Information Commissioner's Office Licence Number: PZ2329565
8. Fitting our Products.
The correct fitting of some or all of our products may require a degree of expertise.
1/ If you are not competent you should seek advice from and/or have the products fitted by a reputable Garage or Car Body Shop.
2/ Where available, all of our products are supplied with fitting instructions.
3/ Lighting products should be professionally fitted and aligned on your vehicle in accordance with the provisions of the Road Traffic Act.
4/ Body Kit Limited are not liable for any costs incurred through the fitting or removal of our products.
5/ Body Kit Limited are not responsible for any loss or damage caused by the use of our products.
6/ You should make sure that any parts are suitable before fitting, Body Kit Limited are not responsible for any installation or removal costs, however caused.
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We use various delivery methods and companies.
Many smaller items are shipped on a 1-3 day delivery service, smaller items are normally sent by Royal Mail first class.
Please note that some items will be sent direct from manufacturers or wholesalers, who will use their own couriers.
We will always deliver your order as soon as possible, delivery estimates are shown within all product details.
Delivery estimates are intended as a guide only.
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We can often deliver many products to other countries, please Contact us for a quote giving as much detail as possible.
10. Availability.
Many of our products are imported and whilst we try to give accurate delivery times, we cannot absolutely guarantee the timely supply of any goods, especially where the delay is beyond our control.
If your goods are not in stock, or there is likely to be a significant delay, we will notify you by e-mail or telephone, and offer you the option to change or cancel your order if you would rather not wait.
We strongly recommend that you do not book workshop time until your goods have been delivered, we will not be held responsible for any losses caused by untimely delivery.
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We take any actual or attempted fraud very seriously, and for security purposes our payment system logs I.P addresses.
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Welcome to www.body-kit.co.uk, the UK number one supplier for all your interior and exterior car styling needs, at unbeatable prices. We stock the best quality ABS Plastic, GRP fibreglass and PUR polyuerathane full and part Car Body Kits, front/ rear bumpers, bumper lip spoilers, front splitters, rear skirts & diffusers, side skirts, rear window covers, roof or boot lid spoilers, head light brows and lowering springs from manufacturers like Lester, Rieger, ICC, P-I (Personal Identity), RGM (Richard Grant Mouldings), Auto-plas & Momo. We also stock the very latest designs in Custom Lighting, headlight bulbs, standard & LED Bulbs, including Angel eyes, Audi style, DRL headlights and HID kits. Chrome, Paintable & LED Universal Door Mirrors and glasses - Z2 (SLR Style), M3 style, DTM style, EVO M6 style & GT-R look door mirrors, from Ultra and Auto-Art. We are appointed stockists of the Race-Sport & Momo Design- Italy ranges of sport alloy road wheels & performance tyres and quality styling products. Our ever growing universal fitment range includes interior and exterior tuning and styling products including, Performance Exhaust Boxes and trims, Air Cleaners, Race style Engine Monitoring Gauges and Mounts, Aerials, Seat Covers, Gear lever knobs and leather gaiters, leather hand brake gaiters and knobs, pedal sets, chrome styling trim, seat covers. We stock an extensive range of chrome, stainless steel and carbon fibre look styling products, and we add to our range all the time. Our latest addition is high quality 9 & 16 mm snow chains and Hi-Tech fabric 'snow socks' for safety driving in the snow and ice.
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The Old Timer of Royal Oak, Mich., was a regular contributor to H&P years before we ever even heard of the internet. But most of his advice is just as useful — and interesting — today.
So rather than leave his wisdom printed on pages archived in our storage room, I pulled out issues from the late 1980s and early 1990s and have been reproducing relevant entries in this blog. Here is my 20th entry, which was originally published in the August 1989 issue:
Water to the Rescue
At one of our aluminum die casting plants, 42-wheeler trucks loaded with molten aluminum in huge kettles entered through the remote North Gate. A heavy-duty concrete roadway provided a path to the plant for these monsters, but every now and then one of the drivers would misread a curve near the gate and run off the pavement. We kept a large Cat tractor on standby to help pull these trucks out, but if they were mired in badly or had blown a tire or two, it was a real race with the clock because the aluminum would harden after about an hour and the expensive load became a total loss.
This was the typical kind of problem that management loved to dump onto the Hydraulics Dept. "We need a portable 80-ton jack for the North Gate area so we can lift the truck beds and slip some railroad ties under the wheels before dragging them out of the mud. Do it cheap because there's no money for this project."
A visit to the North Gate revealed—as expected—that no compressed air or hydraulics were available there. Utilities consisted of 110-V electricity for lights and a 2-in water main for the large flower beds that were the plant manager's pride and joy.
Could we use water pressure to jack up those monster trucks? We learned that water pressure was 60 psi most of the time, 50 psi the rest. To lift 80 tons with 50 psi, we'd need 3200 in.2 of piston area. Wow, a real whopper!
We went looking in the boneyard and actually found a 6-ft diameter squeeze cylinder discarded from a sand line. The tag said "150-psi air or 500-psi hydraulic." With more than 4000 in.2 of piston area, theoretically, we had a 100-ton jack using 50-psi water. Let's do it!
We mounted the cylinder onto a large sled base (another piece of junk) and borrowed a couple of lengths of soft 2-in. fire hose. We teed into the water main at the gate, piped up some hose couplings and three 2-in. gate valves, and we were in business.
The tractor would drag the sled to a mired truck and push it under the low side. A crew then would roll out the hoses, couple them into the system, and turn on the water. The jack extended, the truck lifted, and the crew shoved some ties under the wheels. When they were ready to lower, they dumped the water from the jack in the general vicinity of the flower beds. Then, with an assist from the tractor, the truck was off and running.
This arrangement was not really too unusual when you remember that the original 10th-century hydraulic systems all used straight water. In fact, I carried the concept home where I jack up my car with a garden hose and a scrounged 8-in. bore cylinder.


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