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Approximately 20% of patients report persistent and disabling pain following total knee arthroplasty (TKA) despite an apparently normally functioning prosthesis. One potential risk factor for unexplained persistent pain is high levels of pain catastrophizing. We designed a three-arm trial to determine if a pain coping skills training program, delivered prior to TKA, effectively reduces function-limiting pain following the procedure in patients with high levels of pain catastrophizing.
The trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain coping skills training arm, an arthritis education control arm or usual care. Pain coping skills will be delivered by physical therapists trained and supervised by clinical psychologist experts. Arthritis education will be delivered by nurses trained in the delivery of arthritis-related content. The primary outcome will be change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale score 12 months following surgery. A variety of secondary clinical and economic outcomes also will be evaluated.
The trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain coping skills training arm, an arthritis education control arm or usual care. Pain coping skills will be delivered by physical therapists trained and supervised by clinical psychologist experts. Arthritis education will be delivered by nurses trained in the delivery of arthritis-related content. The primary outcome will be change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale score 12 months following surgery. A variety of secondary clinical and economic outcomes also will be evaluated.
Trial Registration
Keywords:Knee; Arthroplasty; Coping skills; Pain; Catastrophizing
Pain is the predominant complaint of patients seeking total knee arthroplasty (TKA) [1-3], a common and generally effective procedure for patients with advanced knee arthritis [1]. Kurtz and colleagues estimated that in 2010, surgeons would perform over 700,000 TKA procedures in the US and projections suggest 3.5 million TKAs annually by 2030 [4]. Cost data for TKAs also are impressive. Mean procedural and rehabilitation costs per patient, reported in 2006 dollars, were approximately $20,700 per primary surgery and $24,500 per revision surgery [5] plus significant patient costs incurred over 12 months following surgery [6].
Serious early surgical complications such as pulmonary embolism or joint infection lead to poor outcomes. However, the incidence of these adverse events is very low - approximately 2% of all surgeries. Failure of the prosthesis is typically a late complication occurring years following the surgery and accounts for approximately 5% of poor outcomes [7]. The large majority of "poor" outcomes following knee arthroplasty are attributed to disabling pain and impaired function that is not related to early complications or prosthetic loosening. In large patient samples, improvements in pain or function scores have consistently been on the order of 40% to 60% relative to baseline, from 6 months to 2 years postoperatively [8-16].
However, some patients respond poorly to the surgery. For example, Puolakka and colleagues found that 36% of 433 patients reported daily disturbing pain four months or more after surgery [17,18]. Hawker et al. reported similar estimates 2 to 7 years following arthroplasty [19]. Only a third of patients report no functional problems following surgery [20] and approximately 20% report dissatisfaction with their functional ability a year or more after surgery [21]. Functional deficits following surgery are observed in a wide range of activities, with up to 40% of patients still requiring the use of an assistive device to ambulate [19]. Most recently, Beswick and colleagues reported in a systematic review that 20% of patients in high quality cohort studies reported persistent function-limiting pain six months or more following TKA [22].
Disabling pain and reduced function is a large and as yet unsolved problem that has a dramatic impact on quality of life and productivity. For example, revision surgery rates are influenced by persistent pain and impaired function. Roberts and colleagues conducted a survival analysis of 4,400 patients with knee arthroplasty and found that 15 years following surgery, a total of 239 knees required revision and up to 35% were for unexplained pain. Extrapolating to current estimates, as many as 35% of 55,000 revision arthroplasty surgeries in the US in 2010 may be attributable to unexplained persistent pain and subsequent poor function [23].
A barrier to improving postoperative outcomes is that traditionally, knee arthroplasty has been presumed to be a highly effective procedure. TKA perioperative protocols have historically not incorporated routine screening for patients at-risk for post-surgery persistent pain or compromised function because this area has not been scientifically investigated. This culture has strong potential for change, however, because recent research has begun to acknowledge that unexplained poor outcomes occur [22]. Predictors of these poor outcomes following knee arthroplasty have been identified [24-27]. Among the most consistent and powerful psychological predictors of poor outcome following knee arthroplasty is pain catastrophizing [17,26,28-32]. Individuals who catastrophize tend to ruminate about pain, magnify the threat value of pain and feel helpless when dealing with pain [33,34].
Additional impetus to address the issue of persistent pain was proposed by the National Institutes of Health (NIH). An NIH consensus panel was convened to review existing evidence regarding the use of knee arthroplasty surgery and to make recommendations for future research to improve the care for these patients [1]. The panel placed high priority on research examining the impact of perioperative interventions for these patients. Our trial will specifically target this research need. If a high-quality trial demonstrates that pain coping skills training is successful at improving outcomes for at-risk patients with poor pain coping, and is cost effective, current clinical practice paradigms could be significantly improved.
The primary aim of our study is to assess the efficacy of a physical therapist-delivered pain coping skills training program in reducing knee pain and improving function. Our two primary hypotheses are that in patients scheduled for knee arthroplasty and with comorbid pain catastrophizing: (1) Pain coping skills training is more effective than arthritis education in decreasing knee pain during functional activities, and (2) Pain coping skills training is more effective than usual care in decreasing knee pain during functional activities. We also will examine two sets of secondary hypotheses: (1) Pain coping skills training is more effective than arthritis education or usual care in improving self-reported function, physical performance, pain intensity, pain catastrophizing, and patient global ratings of improvement and (2) Pain coping skills training will reduce direct medical costs and indirect (i.e. patient time) costs relative to arthritis education and usual care. We hypothesize that, in addition to accounting for costs associated with pain coping skills training, the intervention will be cost saving or cost-effective relative to arthritis care education and usual care as measured by the incremental cost per quality-adjusted life-year. We will also determine if treatment benefits are mediated by changes in pain catastrophizing: We hypothesize that treatment-related changes in pain catastrophizing will mediate treatment-related improvements in pain and self-reported function during recovery.
Study design
The KASTPain Trial is a three-arm randomized trial (see Figure 1) funded by the National Institute of Arthritis, Musculoskeletal and Skin Diseases/National Institutes of Health (1UM1AR062800). The investigators, research assistants assessing outcomes, and patients assigned to two of the three study arms will be blinded to group assignment. Potential subjects will be informed that they will be randomly assigned to one of two different educational treatments or usual care. They will likely not know whether they will be receiving the treatment with the hypothesized key ingredient (pain coping skills training). The protocol conforms to the CONSORT guidelines for nonpharmacologic interventions [35]. Human subjects approval for the study has been obtained from the Virginia Commonwealth University Institutional Review Board (HM14326).
Figure 1. Legend: The figure illustrates the flow of subjects through the trial.
Study population
We will recruit 402 patients who consult with participating orthopaedic surgeons in one of four sites for TKA. These sites are: (1) Virginia Commonwealth University in Richmond, Virginia; (2) Southern Illinois University in Springfield, Illinois; (3) Duke University in Durham, North Carolina; and (4) Wake Forest University, Winston-Salem North Carolina. To be eligible for participation all patients must: (1) be able to read and speak English and provide informed consent; (2) be 45 years or older; (3) have a diagnosis of osteoarthritis as determined by the patients' orthopaedic surgeons; (4) be scheduled for an elective unilateral total knee arthroplasty no sooner than 2 weeks or later than 8 weeks from the time of recruitment; and (5) score of ≥ 16 on the Pain Catastrophizing Scale and ≥ 5 on the WOMAC Pain scale. Scores of 16 or greater on the Pain Catastrophizing Scale suggest at least a moderately severe pain catastrophizing while scores of ≥ 5 on the WOMAC Pain Scale suggests greater than minor function limiting pain. Patients will be excluded if they: (1) are scheduled for revision arthroplasty surgery; (2) are unable to or decline consent for study participation; (3) have a self-reported diagnosis of inflammatory arthritis (i.e. rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosis, ankylosing spondylitis); (4) have TKA scheduled because of a fracture, malignancy or an infection; (5) are scheduled for bilateral TKA; (6) are scheduled for unicompartmental arthroplasty; (7) report plans to undergo hip or knee arthroplasty within one year after current TKA; (8) underwent contralateral knee arthroplasty surgery or hip arthroplasty surgery within 1 year of currently planned surgery; or (9) score 20 or higher on the Patient Health Questionnaire-8 (PHQ-8) depression screener which indicates likely severe depression [36,37]. Pregnancy is an "automatic" exclusion because women who are pregnant are excluded by their physicians from TKA.
All patients scheduled for TKA with orthopaedic surgeons who conduct at least 50 TKAs per year at one of the four university-based study sites will potentially be eligible for study. We will only recruit surgeons who conduct ≥ 50 TKAs per year because of the potential influence of TKA volume on outcome [38]. Following an opt-out period, each patient will be contacted by phone to assess for eligibility after providing verbal consent for screening. All patients enrolled in the study will attend an in-person session to read and sign the consent form and complete pre-operative data collection procedures. In addition, all patients will complete a series of performance-based measures which include a 6-minute walk test [39] and the short physical performance battery [40], which includes a series of tests of walking speed, balance and strength.
Two in-person data collection sessions will occur for each patient, one at the baseline visit and the other at 1 year following TKA. In addition, staff that are blinded to group assignment will contact patients by phone at 4 different time points; 1 week prior to and 1 week following TKA, 2 months, 6 months following TKA (see Figure 1) to collect outcome data. Key measures obtained at each time point will be the Pain Catastrophizing Scale, the WOMAC Scale, and a knee pain rating scale [42].
Randomization and allocation concealment
All eligible subjects will be randomized following baseline data collection into the pain coping skills arm, the arthritis education control arm or the usual care arm. Patients will be blinded to study hypotheses and will be informed that the study is examining the potential benefits of two approaches to improve outcomes as compared to usual care. The study statistician will prepare a random numbers table to permit randomization in permuted block sizes of 3 and 6, stratified by surgeon. To conceal randomization, assignment will occur via the web interface only after all baseline data are collected. The physical therapists delivering the pain coping skills and the nurses delivering the arthritis education cannot be blinded.
Participants randomized to one of the two treatment arms will receive eight 1-hour sessions of one-on-one instruction to be delivered over a 2-month period beginning approximately 2 weeks prior to surgery and ending 6 weeks following surgery. The first session will be delivered in-person and subsequent sessions will be delivered via the telephone. Telephone-based behavioral interventions for pain management have been shown to be effective [42,43].
Pain coping skills
The 8-session pain coping skills training (CST) will be delivered over a 2-month period by physical therapists. This number of sessions of CST has been shown to be effective in several behavioral trials [44-50]. Study physical therapists must have practiced for at least 2 years and reported experience in the treatment of patients with TKA.
The (CST) protocol will: (1) provide a rationale for the coping skills intervention; (2) train patients in cognitive restructuring as well as a variety of skills that provide patients with opportunities to observe the impact of coping skills on changes in negative pain-related cognitions typical of pain catastrophizing (i.e. thoughts related to pain rumination, pain magnification, and helplessness in the face of pain); and (3) provide training in strategies for enhancing maintenance of gain following treatment. Melzack and Wall's gate control model of pain will be used to help patients reconceptualize their pain and emphasize their own abilities to control pain. The gate control model highlights the role that thoughts, feelings, and behaviors can play in influencing the transmission of noxious signals from the periphery to the brain [51]. Training in pain coping skills will be described as a way of changing thoughts, feelings, and behaviors that contribute to pain.
Using techniques drawn from cognitive therapy, patients will be taught how to identify irrational, maladaptive, and catastrophic pain-related thoughts and to replace these with alternative, rational, reassuring and adaptive thoughts [52]. Self-instructional training will be used to teach patients how to use calming self-statements as a way of coping with pain flares [53]. Activity-rest cycling and pleasant activity scheduling [54-56] will be used to help patients increase their activity level and observe the resultant impact on their pain-related cognitions. Activity-rest cycling teaches patients to target activities they tend to overdo (e.g. prolonged standing or walking while shopping) and learn to break these activities into periods of moderate activity (e.g. 30 minutes of shopping) followed by a limited rest break (e.g. 5 minutes of rest). Over time, the goal is to help patients raise their activity level by increasing the length of their activity and decreasing the length of their rest periods. In pleasant activity scheduling, patients learn how to identify activities they enjoy doing (e.g. reading, doing hobbies, and visiting friends) or that give them a sense of mastery (learning how to do something new such as typing or a new language) and then set and record weekly activity goals.
Patients also will be trained in three attention diversion methods that can be used to alter negative pain related cognitions: relaxation, imagery, and distraction. Progressive relaxation training [57] will help patients learn to concentrate on muscle tension signals and use them as cues to relax. Patients will be taught how to use pleasant imagery as a way to alter their pain-related thought patterns and foster relaxation [58]. Distraction training will involve training in how to focus on physical stimuli (e.g. a photograph or picture of a nature scene) or auditory stimuli (e.g. listening to music) when experiencing increased pain [58]. Using relapse prevention methods, each patient will develop a written maintenance plan that includes the list of pain coping skills learned during the study, potential high risk situations, early warning signs of setbacks, and plans about how the patient might apply these skills in dealing with future setbacks and challenges. Table 1 highlights the key elements of the CST protocol.
Table 1. Components of the pain coping skills intervention
Arthritis education
Patients randomly assigned to the arthritis education arm will receive detailed information from a registered or licensed practical nurse educator about osteoarthritis and its treatment. The arthritis education intervention will control for participation in a trial, time and clinician attention. The arthritis education sessions will use a presentation and discussion format similar to that originally described by Lorig for arthritis education [59-62]. Figures and discussion sessions will present information on the nature of arthritis, the post-operative course of knee arthroplasty, treatment of osteoarthritis, the role of exercise, joint protection and making future treatment decisions.
This general approach to an arthritis education comparison condition has been used successfully in many behavioral studies and in several trials conducted by Keefe and Jensen [44-50,62]. An education comparison condition is a credible treatment and allows us to test whether the "pain coping" component of the experimental intervention is the specific treatment element that reduces pain and improves function over that seen in patients who receive a similar dose of time and attention from a health professional, but no training in pain coping skills.
Usual care
We have added a "usual care" group to determine real world effects of pain coping skills. Patients in the usual care group will only receive care that they would have routinely received had they not been entered in the study. All patients in this group will undergo the same data collection procedures as patients in the other two treatment arms with the exception of the eight treatment sessions.
Patients are routinely prescribed medications for pain control and are referred for physical therapy following TKA. Data regarding medication and extent of rehabilitation therapies will be tracked throughout the study period and will be adjusted for, if necessary, in the analyses.
Treatment adherence and fidelity
Because multiple study sites will participate and increase the risk of low fidelity due to differing approaches in applying the interventions, the research team will take a number of steps to ensure that the treatment protocols for CST as well as arthritis education are delivered uniformly by all treatment providers involved in the study. First, all pain coping skills training will be delivered by physical therapists with at least 2 years of clinical experience including the treatment of patients following TKA. Second, all physical therapists will receive coping skills training in a 2-day workshop delivered by clinical psychologist experts at Duke University. Experienced nurse educators will all be trained in 2-day workshops by DLR, a physical therapist with 30 years of experience and research in arthritis and rehabilitation, to provide the arthritis education. Third, all physical therapists and nurse educators will be provided with detailed treatment manuals and the treatment strategies will be taught through didactic instruction, illustrations of techniques from model cases, and role-play of common scenarios. Fourth, we will institute several "best practices" to enhance and monitor treatment fidelity of the pain coping skills training and arthritis education which include: (1) careful attention to the study design; (2) intensive training; (3) role playing of treatment skills enactment during training; and (4) on-line documentation of treatment delivery. All sessions for both groups will be audiotaped and supervisors or investigators will review tapes periodically for each physical therapist and nurse educator during the study. Remedial training will be provided for those clinicians who deviate from established protocol.
The primary outcome measure and endpoint will be the WOMAC Pain score measured 1 year following knee arthroplasty [63-67]. The WOMAC has been studied extensively and its scales have been shown to be reliable and valid for quantifying the extent of both pain and disability in patients undergoing knee arthroplasty [16,68,69]. Secondary outcome measures will be the WOMAC Disability scale, Pain Catastrophizing Scale (PCS) [33,70,71], a verbal pain rating scale [72,73], and a patient global rating of change scale measured on a numerical rating scale from -5 (vastly worse) to +5 (completely recovered) [74-76]. All outcome measures are summarized in Table 2. Outcomes will be measured pre-operatively, 2 months, 6 months and 1 year post-surgery. To assess for potential mediating effects of pain catastrophizing on outcomes, the PCS and WOMAC scales will be administered one week prior to and 1 week following TKA. Two performance-based measures, the 6-minute walk test [39,77] and the Short Physical Performance Battery will be assessed at baseline and 1 year post-surgery [40].
Table 2. Summary of primary and secondary outcome and cost measure
Power considerations and data analysis
The primary endpoint will be the WOMAC Pain score at 1 year. Changes of 2 or more points in the 20-point WOMAC Pain scale indicate clinically important differences in pain-related function between individual patients [78-81]. We powered the KASTPain study to detect a difference of at least 2 points between the mean pain scores in the pain coping skills group and the arthritis education group [82].
Using a two-sided, two-group t-test of differences in means with alpha set at 0.05 and assuming the intervention difference minus the arthritis education control difference is at least 2 WOMAC Pain points, a sample size of 107 in each group will provide 91% power to detect this difference, assuming that the common standard deviation is 4.34 (based on pilot work). This corresponds to a moderate effect size of 0.46 which is consistent with the effect of other behavioral interventions for knee arthritis [83-85]. This sample size also provides 80% power to detect a 20% difference between groups in the proportion of patients with a 50% or greater improvements in WOMAC pain relative to baseline scores [9,10,12-15,86]. This effect is equivalent to an odds ratio of 2.25 and a number needed to treat (NNT) of 5 [87].
The required sample size is 321 (107 patients per arm) for the planned three-arm trial. Based on our pilot study, we expect 5% attrition due to early drop-out resulting from cancelled surgery. Patients who undergo surgery and drop out due to lack of interest, unrelated medical illness or loss of follow-up will be included in the intent-to-treat analysis. Our previous work with similar types of patients suggests that loss to follow-up will likely be approximately 20% one year following surgery [14,30]. Therefore, 402 patients (134 patients per study arm) will need to be enrolled in the trial. The accrual and retention numbers will be monitored during the study to assure that sample size estimates are reached. Stratification by surgeon is expected to reduce outcome variability and thereby increase power.
Intention to treat (ITT) will be the primary approach for all analyses. Because we expect that some patients will provide consent for our study but may opt out of surgery for a variety of reasons, we will compare the ITT analysis to the results for patients who actually undergo surgery (i.e., attrition analysis). For the primary analysis, the effect of treatment will be assessed using linear mixed models with time as a repeated factor. The model will account for correlation over time within participants, correlations within surgeons, and baseline covariates. Surgical approach, complications, medication and physical therapy use will be assessed for potential effects. Restricted maximum likelihood method (REML), which uses all available data, will be used to estimate the linear mixed model. REML is the default option in multiple software packages for mixed models including SAS and Mplus. Wothke has shown that no other missing data handling method, regardless of missing data mechanism, performs better [88].
Estimates of the effect of pain coping skills training will be obtained by constructing linear contrasts to compare the outcome at each of the key time points (baseline, 2 months, 6 months and 1 year) between the pain coping skills group and the two control groups, with adjustment for the other variables. Analyses of the secondary outcome variables will be conducted using a similar approach. For the analyses using dichotomous outcomes of ≥50% improvement at 6 months and 12 months, generalized linear models with logistic regression will be used to compare the proportion of patients with ≥50% improvement after adjustment for covariates.
As an additional secondary analysis, we also will examine the effects of potential moderators. Moderators are patient characteristics that predict treatment effects [89]. Additional psychosocial issues may influence treatment effects in knee arthroplasty. Potential moderators for patients with knee arthroplasty who may particularly benefit from pain coping skills training are the following: treatment expectations prior to surgery [90-92], self efficacy [93,94], extent of social support [9,95] and depression [28]. Because our study is not powered to test for these potential moderators, they will be assessed in the context of hypothesis generation rather than hypothesis testing and only for the primary outcome of WOMAC Pain at 1 year. This analysis will be performed by including a two-way Moderator X Treatment group interaction term in the mixed models analyses. We will assess whether these variables independently predict those patients who are more likely to respond to pain coping skills training versus arthritis education or usual care. Pain coping skills training emphasizes pain coping strategies, unlike usual care or arthritis education and because of this emphasis, we suspect that coping strategies training will be particularly effective in patients with adverse psychosocial characteristics. Knowing whether any of these potential moderators actually predict response to treatment may aid in better identifying individuals who are more likely to respond to the intervention.
Economic evaluation
Medical resource use and total costs
We will also compare medical resource use and mean total costs incurred over the one-year follow-up period in the KASTPain study between patients randomized to coping skills training vs. arthritis education vs. usual care. Counts of medical resource use will include inpatient stays, outpatient visits to physicians, physical therapists and other providers, and days of pain medication. Sources for unit costs assigned to medical resource use will include average Medicare payments for inpatient care and outpatient services and average wholesale prices published in the Red Book for medications. The TEAM-HF Costing Tool will be used to estimate intervention costs by accounting for providers' time spent delivering the study intervention [96]. Total costs will consist of direct medical costs associated with the study interventions and costs associated with TKA, rehabilitation, complications and pain management as well as patients' time costs associated with receipt of the study interventions. Total costs, from the societal perspective, will consist of direct medical costs, intervention-related costs and indirect costs. From the health care system (or payer) perspective, indirect costs will be excluded. Sensitivity analyses will be performed to evaluate the impact of scaling up the intervention (i.e. more patients per session; fixed costs allocated over more patients) and methodological choices for cost assignment [97,98].
Cost-Effectiveness analysis
A cost-effectiveness analysis will also be performed. Incremental cost-effectiveness ratios (ICER) will be calculated as the difference in the mean costs per patient between study arms divided by the difference in estimated quality-adjusted life-years (QALYS). Mean costs will be estimated as described above. QALYs will be estimated using patient-level utility estimates derived from the EQ-5D, administered at baseline, 2 months, 6 months and 1 year [99]. Because the study interventions represent fixed-, one-time costs while the benefits of the interventions may last beyond the one year follow-up period in the KASTPain study, we will conduct sensitivity analyses that extrapolate differences in utilities measured at the end of follow-up over 3, 5, and 10 years, assuming that the interventions do not differentially impact survival. If we observe statistically significant differences in costs (not including costs for the intervention or initial surgery) between treatment arms at 12 months, we will extrapolate treatment-specific cost estimates over 3, 5, and 10 years, consistent with the time period for QALYs. We will evaluate uncertainty by estimating 95% CIs for estimates of costs, QALYs and measures of cost-effectiveness (i.e. ICERs or net health benefits [100]) using nonparametric bootstrapping.
Our study will be the first to examine the efficacy of a pain coping skills training intervention delivered by physical therapists to patients at risk for poor outcome following orthopaedic surgery. The use of physical therapists as interventionists is innovative because the intervention is traditionally delivered by clinical psychologists. However, given the limited availability of clinical psychologists and the large volume of TKA procedures, physical therapists routinely treat patients prior to and following TKA and are optimally positioned to provide coping skills training.
Previous work by our group [30] and others [28,29,32,101] has identified a TKA patient subgroup at risk for poor outcome. Patients with high levels of pain catastrophizing have been consistently shown to have a higher rate of persistent pain and compromised function compared to non-catastrophizers [28,102,103]. Current clinical paradigms do not discuss formal identification of patients at-risk for poor outcome due to ineffective pain coping [104,105] nor do these paradigms address the use of perioperative interventions to reduce poor outcome risk. Our trial will provide high-quality evidence to potentially challenge this practice paradigm. If the KASTPain intervention is effective, the research will provide strong evidence to consider augmenting this traditional approach with a scalable intervention that could improve pain and functioning for thousands of patients with TKA who are at high risk for poor outcomes.
TKA: Total knee arthroplasty; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.; NIH: National Institutes of Health; PHQ-8: Patient Health Questionnaire-8; CST: Pain coping skills training; PCS: Pain Catastrophizing Scale; NNT: Number needed to treat; ITT: Intention to treat; REML: Restricted maximum likelihood method; ICER: Incremental cost effectiveness ratio; QALYS: Quality adjusted life years.
Competing interests
Drs. Riddle, Keefe Ang, Saleh, Dumenci, Jensen, Bair, Reed and Kroenke have no competing interests to declare.
Authors' contributions
All authors participated in the conception and design of the protocol and helped to draft the manuscript. All authors read and approved the final manuscript.
The study was funded by the National Institute of Arthritis, Musculoskeletal and Skin Diseases/National Institutes of Health (1UM1AR062800).
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Charlie Banana 2-in-1 Reusable Diapering System, 1 Diaper and 2 Inserts, (One Size), Robot Boy
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If you always wanted to try a cloth diaper, you will love the Charlie Banana 2-in-1 Reusable Diapering System and its innovative design. The system contains 1 diaper with 2 washable inserts. The diapers adjust to your baby's ever-changing features with a safe-snap system. One size fits babies from 0 to 36 months depending on the baby's size. It's great for everyday and overnight use. Charlie Banana inserts are highly absorbent.
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Beat the Heat With Safe Exercises
Lady of America Franchise Corporation Offers Tips to Exercise Safely in the Sizzling Heat
Ft. Lauderdale, FL (PRWEB) August 22, 2011
With the majority of the country experiencing a dangerous heat wave these past few weeks and no immediate relief in sight, Lady of America Franchise Corporation wants to make sure you beat the heat "• and stay safe "• when it comes to exercising.
According to the Centers for Disease Control and Prevention (CDC), heat-related deaths and illness are preventable, yet annually many people succumb to extreme heat. Though the elderly and ill are at great risk from the heat, so are healthy young people because they do not recognize the dangers of exercising in hot weather "• especially hot, humid weather.
People suffer heat-related illness when their bodies are unable to compensate and properly cool themselves. The body normally cools itself by sweating. When the humidity is high, sweat does not evaporate as quickly, preventing the body from releasing heat quickly. Other conditions related to heat-related risk include age, obesity, fever, dehydration heart disease, mental illness, poor circulation, sunburn and prescription drug and alcohol use.
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Stay hydrated. Before exercise, drink 8 ounces of water 30 minutes prior to the start of your workout. During exercise, drink 3 to 6 ounces of water every 15 minutes. After exercise, drink 8 to 16 ounces of water within 30 minutes following your workout.
Dress appropriately. Wear lightweight, moisture-wicking or loose-fitting clothing that allows the sweat to evaporate from your skin. Choose lighter colors because they won't absorb as much heat from the sun, and wear a hat or a visor to keep the sun out of your eyes. To keep your feet dry, choose lightweight cotton socks.
Watch your heart rate. When training in the heat, you don't need to work as hard to elevate your heart rate. Closely monitor your heart rate during outdoor exercise; adjust your pace accordingly.
Avoid the hot zone. Avoid exercising outdoors between 10 am and 3 pm, as it is said to be the hottest part of the day. Early morning or late evening may offer cooler temperatures. If you exercise during the hot zone, consider scaling back on the duration and intensity, and find an area that offers shade (parks, trails, etc.).
Take it indoors. Exercising indoors at your local Lady of America Fitness Center provides protection from the heat.
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Lady of America Franchise Corporation wants you to be prepared at all times. Heat-related illness can occur suddenly. If you experience any of these symptoms, Lady of America strongly suggests you get out of the heat immediately, rehydrate and rest, and seek medical attention if necessary.
About Lady of America Franchise Corporation
For more than 27 years, Lady of America Franchise Corporation (LOAFC) has been an innovator in the constantly evolving business of women's fitness. LOAFC was established in 1984 with the goal of providing a safe and rewarding environment to women working on their fitness and lifestyle goals while enjoying the company and support of other women. The company continues to host fun fitness and exercise challenges. Today, LOAFC is the world's largest full-service chain of women's fitness centers with 200 franchises in operation across 45 states and nine countries under the brands LOA Fitness for Women, Lady of America, Ladies Workout Express, Workout Express and HCOA Fitness.
For the original version on PRWeb visit: http://www.prweb.com/releases/prweb2011/8/prweb8737243.htm


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|97 posts found
Originally posted by Aelious
i would argue the success of guild wars 2 and the adaptation of all other games wow included says that alot more people than ever before are spending time to become someone elses content.
ultimately, people need to provide the content, How exactly to accomplish it is debatable of course.
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Elite Member
Joined: 9/27/11
World > Quest Progression
Originally posted by rungard
I agree completely and what I was envisioning was pockets of WvW from GW2 but with some regional backstory between the factions/races that were in the area. The success of WvW shows that if you give people the option of doing PvPvE a lot more will take it than forcing PvP on those who usually enjoy PvE.
One reason why balancing PvP and PvE is difficult is because the combat, content and the objectives are so different. If you can bring those closer together, you'd have easier time balancing the game. This would mean smarter AI and no threat minigames among many other changes.
I skate to where the puck is going to be, not where it has been -Wayne Gretzky
Originally posted by Quirhid
I agree, but the smartest AI is a player(theoretically), and the next best thing to that is a player who has limited abilities to direct the ai and initiate events in an unpredictable way. Thats true dynamic.
whether you like guild wars 2 or not, they have a nice event system in their game. Whats the problem with it? Its static. Do it over and over and over again.
What if, it were possible for a player on the opposing side could initiate a pve event upon pve players. We couldnt have half the server doing this, it would be chaos, but we could have a very small proportion of the players doing these kinds of things. It doesnt mean they cant happen on their own, its just a dynamic enhancement to the system.
the fact that these players could take part in the events as well would be equally as interesting.
the gameplay options are staggering, not just for pvpers but pvers as well.
people are too focused on ganking when in fact these players would be great assets to any pve game.
Novice Member
Joined: 11/18/04
Heroes are about character - not gear.
Originally posted by Quirhid
Start with the Player, then PvP, and then PvE. Why that order? Well, it's about trying something other than starting with the PvE, then the Player, and finally PvP. Because that obviously does not work, eh?
The objectives are not really that different, imo - not in the least. Objective - kill the enemy. It's pretty much the same.
The problem arises with the initial focus on PvE creating ludicrous stats and munchkin characters which leads to mind boggling PvP. It's not a balanced focus.
If on the other hand, you focus on the Player first - you lay out the path that you want for the various classes/skills/etc - you've got a solid base for going into PvP - and - you also have that solid base for going into PvE.
It would provide us something other than the illusion of difficulty - as we're fighting level 1000 mobs that are basically just level 1 mobs with more health and more damaging attacks. In some cases, it's exactly like that...meh.
As for the mobs, I'm still waiting for somebody else to tackle it via something similar to AD&D's Challenge Rating. Something where the mobs are actually an appropriate challenge rather than just part of the ongoing crop of monster farms that we see. Even with this, there would still be room for threat - but it would have to take into consideration the intellect of the mobs. Some would be too smart for it, some would be too stupid for it, and some just would not bother with it. There would be a limit as well - in that one could not grab aggro on a million mobs.
And the more I think about all this, the more I know that it will never happen...because it's not about making a game for the single player where they can feel like a god - which I'm hard pressed not to see in most games. So it's kind of pointless to share any further thoughts on it...
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Originally posted by coretex666
I'm looking from the same perspective that my OP starts with.
This isn't a fight, its a civilized argument, and you are trying to discuss a topic that I didn't raise.
I never, in any of my posts, defined a PVE oriented game (or even attempt to do so). I was directly, and specifically adressing WoW in the context I provided and you brought up.
GW2 has PVP and PVE separated, yes, and thats why now the PVE feels tacked on. People are bitching about there being no PVE endgame (i.e. what to do at lvl-cap and have no interest in pvp).
Regardless of your feelings for WoW PVP, its not a PVP-centered game.
You seem to be confused what PVE- or PVP-centered means. The mere existence of a feature doesn't make something PVE or PVP-centered.
A PVP centered game, like EVE, has all mechanics crafted around PVP. All its aspects flow into PVP.
You craft gear for PVP, you mine to support your alliance, you do PVE (ratting) to acquire resources to do PVP, you research for PVP, even if you just run the economy, you still support PVP because the economy and resources is what the PVP centers around (via PVP-death as resource-sink).
WoW PVP is mechanically separate from the game WoW PVE.
Originally posted by VirusDancer
I think you underestimate its effect. Often it is more than just killing the enemy and secondary objectives can have a huge effect on how you go about doing that. You'll also notice that rarely the killing is the primary objective in any PvP: It is usually holding some capture point, protecting something or someone, stealing something etc. Killing is in fact often a secondary objective or a simply a means to achieve the primary objective.
Some PvP objectives (secondary and primary) also require specialized roles. For example a flag runner has to be mobile and fast. In PvE, players pretty much specialize in killing stuff quickly and efficiently - thats about it.
Bringing PvE and PvP closer together is a simple idea, but the more you think about it the more complicated it gets and more profound changes you need.
I skate to where the puck is going to be, not where it has been -Wayne Gretzky
Originally posted by rungard
Its not really fair to call them static since not all of them are that - more like cyclical in nature. The events, I think, are infinitely better than traditional quests. A comfortable start towards better "questing" atleast.
Now they just need to expand the web-like structure of the events and add more, multiple-ending events with branching event-chains.
The events already offer rudimentary objectives to PvP and I think they could and should be developed a little more. I'm not an advocate of mixing PvE and PvP tho.
I skate to where the puck is going to be, not where it has been -Wayne Gretzky
Novice Member
Joined: 11/18/04
Heroes are about character - not gear.
Originally posted by Quirhid
I used the term killing to represent beating. The objective is to beat the enemy. Every PvP scenario can be a PvE scenario. Every PvE scenario can be a PvP scenario. In many games, the PvE scenarios are common FPS scenarios where you're fighting mobs instead of players.
I miss the MMORPG genre. Will a developer ever make one again?
Explorer: 87%, Killer: 67%, Achiever: 27%, Socializer: 20%
Novice Member
Joined: 2/27/08
I hate PvP with a passion, I want nothing whatsoever to do with it, ever. That said, so long as I can entirely ignore it, I don't care if people want to go do PvP somewhere I don't have to watch the childish dickwaving.
But given a choice, I'll take pure PvE with no PvP whatsoever.
Played: UO, EQ, WoW, DDO, SWG, AO, CoH, EvE, TR, AoC, GW, GA, Aion, Allods, lots more
Originally posted by VirusDancer
I was wondering the same thing recently actually.
Why cant more games have human controled scenarios? It doesn't really need to be even called PVP (because that apparently has a very specific connotation).
How about a system where one part of the game is played strategically, the other from the individual perspective. What if the PVE scenario would be controlled in an RTS fashion by a DM?
I mean, thats what DMs are for in tabletop RPG, but its not considered PVP certainly.
People don't play DnD vs the DM, they play vs the world, controlled by the DM.
There seems to be a point at which players are able to disconnect from the "perception of PVP".
Imagine a raid scenario where the boss is controlled by a DM, would that be considered PVP? By most people certainly not.
I need to think more about that, but it might have to do with asymetrical ballancing and how players perceive entity-control and fairness.
Example: The game Dungeonland
PvE leveling process, PvP endgame.
Hard Core Member
Joined: 4/30/09
Originally posted by AdamTM
I would first like to know what is your definition of "pve"?
Do you just mean dungeons, or does that also encompasses crafting and economy?
If so, I would say that it is possible to create a game that has both equally good, like for example SWG pre-NGE.
However if you define PvE as in raids and dungeon, than I would say I prefer pvp-centric.
Originally posted by AdamTM
Not completely, but merely two differnt game experince within a single game, just like a single player adventure game will have a different feel from a multi-player varient of the same game. Having two seperate games would be more like wow bgs, arenas, and such that only effect a small degree of the world, and having stats that you can stack to influence that one style of play over another like resilence. Where as making the abilities having seperate values that influence differing playstyles allows the game to be balanced better from a dev side as players can not influence these values, and allow for them to work largely in the same manner with differing degrees of power without breaking the other style playy. Though in the end pvp an pve will alway be seperate gaming experinces, from the fact a mob will always be less unpredicatable then another player will be, but not completely seperate game that can not be merged with into a singular game. You could also call it more of a game with seperate rule-ssets to govern oppossing styles of play, but the game would still be the ssame at it's heart as you would not have to make game altering change to it to keep balance, as the game from the launch wa built to be balanced seperately behind the scene/under the hood.
Originally posted by aRtFuLThinG
PVE would encompass strictly guided or nonguided combat VS AI-controlled opponents in a non-direct non-competitive way.
Ratting in EVE is PVE content for example.
Originally posted by Asuran24
Mechanically they would be however two separate games.
Sure, you could try and weave them together in the world, but they always be separate, like you said.
Thats why I implied that it would be better to separate them entirely.
There is more to PVP than just stats. Maps, level-design and objectives can play a big role in PVP as well.
The developer would need to dedicate resources to track both gameplay styles and cater to both audiences, which often ends in one being neglected over the other.
[EDIT] I think that most developers actually considered this system long ago but thought it not worth their effort and resources and opted instead to have separate "zones" or contained instances for PVP, simply because they are easier to control. At least in "modern" MMORPG design.
all a company has to do is make a great game with a great integrated pvp ruleset and demonstrate that you wont be ganked in the early levels and most players will forget about the shoddy implementations they may been exposed to (or may only heard about).
the days of 100% pve are coming to a close for one reason and one reason only.
pve content is very expensive to create, pvp content is quite cheap.
its already started. we are in the phase where its kept seperate to get people used to it.
its still a waste of resources because you have to do everything twice.
That is not the last phase.
Novice Member
Joined: 8/17/09
"A very special kind of stupidity"
Originally posted by AdamTM
Fundamentally, I log into an MMO (rather than start up a single player game) to interact with other humans, not to smoosh computer-controlled sprites.
I can't imagine why people would want an MMO with no PvP. It'd be like sleeping with a girl with one leg; even if that leg was in great shape and had a silk stocking, and the girl's face was really pretty, and she was really good at hopping, you'd still be intensely aware that something important was missing.
Give me liberty or give me lasers
Originally posted by Malcanis
Somehow i think this analogy has no leg to stand on.
Novice Member
Joined: 8/17/09
"A very special kind of stupidity"
I also considered extending the analogy by noting that some people only want to undertake activities that they're guaranteed to succeed at because they don't like too much real challenge, but that might have stepped outside the bounds of good taste.
Give me liberty or give me lasers


text:
Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/6229
|Patterns and predictors of fast food consumption after acute myocardial infarction
|Other Titles:
|Patterns and predictors of fast food consumption with acute myocardial infarction
|Salisbury, Adam C.; Chan, Paul S.; Gosch, Kensey L.; Buchanan, Donna M.; Amin, Alpesh; Spertus, John A.
|University of Missouri (System)
fast food
acute myocardial infarction
|Background: Fast food is affordable and convenient, yet high in calories, saturated fat and sodium. The prevalence of fast food intake at the time of acute myocardial infarction (AMI) and patterns of fast food intake in recovery are unknown. Moreover, the association between dietary counseling at hospital discharge and fast food intake after MI has not been described. Methods: We assessed baseline, 1 and 6-month fast food intake in 2494 patients in TRIUMPH, a 26-center, prospective registry of AMI patients. Fast food intake was divided into frequent (≥ weekly) vs. infrequent (< weekly) consumption. Multivariable regression was used to identify predictors of frequent fast food intake at 6-months, adjusted for baseline fast food consumption, sociodemographics and clinical factors. Results: Frequent fast food intake was common at the time of AMI (36%), but decreased substantially after AMI to 17% at 1-month and 20% at 6-months (p-value <0.0001). Patient characteristics independently associated with frequent fast food intake at 6-months included white race, male gender, health literacy, financial difficulty, dyslipidemia and diabetes. College education, heart failure and coronary revascularization during AMI admission were inversely associated with 6-month fast food consumption. Importantly, dietary counseling at discharge was not associated with lower 6-month fast food intake. Conclusion: Fast food consumption declined substantially after AMI. Certain populations, including patients with financial difficulty and lower health literacy continued to eat fast food frequently after their event. Although several patient groups are at risk for persistent high fast food intake, current dietary counseling efforts appear ineffective at altering behavior and new counseling strategies are needed.
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text:
The Battle of Evesham
August 4, 1265
Evesham, Worcestershire
an alliance of rebellious barons under Simon de Montfort vs. royal forces under Prince Edward (later Edward I).
Montfort and his allies rebelled against what they saw as poor government and excessive spending on foriegn wars by Henry III. Initial success at the Battle of Lewes gave Montfort practical control of the government, and he instituted reforms which eventually led to the English Parliamentary system of government by representation.
However, Montfort was undone by his bickering allies, and Prince Edward escaped from captivity to raise the royal standard on the Welsh Marches. Montfort, carting along the King, marched north, intending to join forces with his son at Kenilworth, near Warwick. Edward got there first, routed the younger Montfort, and surprised Simon at Evesham.
In a story which is likely apochryphal, Montfort, realising that his army was trapped in a loop of the River Avon by a superior force, said to his aides, "Let us commend our souls to God, because our bodies are theirs". He was right.
The Battle
Montfort's already slim chances of breaking through the royal lines was made even more remote when his Welsh allies deserted before battle was joined. This left him facing an enemy with perhaps four times the number of his own troops.
Montfort's men charged uphill against the royal lines, but they never stood a chance. Edward's wings pivoted and converged on Montfort's flanks, and the fight quickly became a massacre.
Even the fleeing Welsh were cut down or drowned in the river. No quarter was given to the rebels, and the carnage was terrible. Montfort's body was badly mutilated and dispersed to different parts of the kingdom. His torso, at least, was sent to Evesham Abbey, where his tomb became a popular pilgrimage centre.
The Results
Evesham marked the end of the so-called Baron's War. A few futile skirmishes followed, but the result was a forgone conclusion. Henry III was restored to power and the remaining sons of Montfort eventually fled the country. Prince Edward also proved himself an able and talented military leader, a fact which his later career in Wales and Scotland certainly bears out.
The Baron's War
Battle of Lewes
More British Battles
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text:
WADA: MLB should toughen on cheats
Updated: January 12, 2010, 4:01 PM ETAssociated Press
LONDON -- The president of the World Anti-Doping Agency says Mark McGwire's admission of steroid use should spur baseball to get tougher on drug cheats.
WADA president John Fahey said Tuesday that despite "incremental progress" baseball's drug program still falls short of the "universally accepted standards" of the international code on doping.
After years of denying he took performance-enhancing drugs, a tearful McGwire apologized Monday. He said he used steroids and human growth ...
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Mark McGwire admitted Jan. 11 that he used steroids on and off for nearly a decade, including during the 1998 season when he broke the then single-season home run record.
- OTL: Wenzlaff calls out McGwire
- OTL: Dealer contradicts McGwire
- Guillen feels betrayed by McGwire
- Jenkins: McGwire owes many apologies
- Fisk blasts McGwire
- Pujols backs McGwire, awaits spring training
- McGwire cheered in first public appearance
- La Russa: 'Clark comments about me wrong'
- Jack Clark: McGwire among MLB 'creeps'
- Canseco insists he injected McGwire
- McGwire admits using steroids
- FBI knew of McGwire steroid use
- Committee chair was aware of PED use
- Cards stand behind new coach
- WADA: Admission should motivate MLB
- Trachsel bugged by Sosa-McGwire hug
- Bryant: The Mark McGwire backlash
- Wojciechowski: A tale of two cheaters
- Johnson: Next confession should be Selig's
- ESPN's Hall of Fame voters speak out
- Jayson Stark: McGwire talks, seems contrite
- Buster Olney: Laced with denial
- Tim Keown: Still not taking responsibility
- Tim Kurkjian: 'A regrettable thing to do'
- Howard Bryant: Better man, still not HOFer
- Gene Wojciechowski: Forming a line of truth
- Rob Neyer: McGwire finally comes clean
- Lester Munson: Taking a legal look
- Mike Fish: FBI knew of McGwire's steroid use
- Jim Caple: More baseball 'revelations'
- McGwire's interview with Bob Ley
- McGwire's interview with Bob Costas
- McGwire makes emotional admission to AP
- McGwire admits steroids use
- Buster Olney, John Kruk break it all down
- Baseball Tonight reacts to McGwire
- T.J. Quinn reacts to McGwire's admission
- Tony La Russa encouraged by admission
- Jose Canseco reacts to McGwire's admission
- Mike Schmidt pleased Mac came forward
- Bobby Knight defends McGwire's legacy
- T.J. Quinn: Holes in the truth
- Jeremy Schaap: What is his legacy?
- Matt Holliday: McGwire still his friend
- Buster Olney: Still no Hall of Fame
- Shaun Assael: Bad timing
- Tony La Russa disappointed, not betrayed
- Rob Neyer: No chance to improve HOF chances
- Mike Golic shares his steroids story
- Dick Vitale: Feeling completely cheated
- Vote: Steroids and the Hall of Fame
- What single-season standards still matter?
- Vote: What's your take on McGwire?
- Fans sound off on McGwire's admission


text:
Accessible travel
Auckland Transport is continually striving to improve services for people with access challenges and those with limited mobility. Through guidance from the Transport Accessiblity Advisory Group (TAAG) we hope to make using public transport in Auckland a positive experience.
Many public transport vehicles in Auckland are able to cater for those with access challenges; however it is advised to contact your bus, train or ferry operator to check before you travel. The contact details for each operator are listed below.
- Find out about bus accessibility information.
- Find out about train accessibility information.
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- Find out about concessionary fares.
Bus accessibility information
- Bus operator contact details.
- Kneeling bus services.
- Wheelchair accessible bus services.
- On request audio and braille.
All bus services welcome passengers accompanied by service dogs or disability assist dogs.
Around 55% of Auckland buses have super low floors and the ability to kneel to meet the curb, or have wheelchair ramps fitted to allow easy access for wheelchair users. New buses are being introduced regularly to increase the number of wheelchair access buses in service.
To ensure that there will be a wheelchair access bus on your bus route at the time you wish to travel, we recommend you contact the operator the day before you travel. Find a list of contact numbers.
For guidance only: Wheelchairs and some mobility scooters can be carried on a bus subject to the following restrictions:
- Maximum length: 1200mm.
- Maximum width: 700mm.
- Maximum weight: 240kg (combined weight of wheelchair and user).
Please note: for safety reasons pushchairs may be required to be folded down before boarding to ensure they can be safely stowed. For space reasons, buses are unable to carry large mobility scooters or some larger style pushchairs and the measurements above should be used for guidance only.
The mobility devices described above are deemed to be for disabled passengers and exclude personal motorised mobility devices, such as Segways, which may not be carried on passenger services.
A row of seats towards the front of most buses is identified as especially available for the elderly or those with access challenges. Please help us make these passengers' journey easier by allowing them to sit in these seats.
Bus operator contact details
|Bus Operator
|Contact details
|Waka Pacific/North Star/GO WEST/Metrolink
|Passenger assistance (to confirm wheelchair access for a specific trip): 09 373 9100
Lost property: 09 373 9118 - press option 2
After hours emergencies: 09 309 6269
|Ritchies Transport
|West Auckland: 09 833 6053
North Shore: 09 415 9138
|Howick & Eastern Buses Ltd
|09 273 3660
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|09 620 5492
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|09 372 8823
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Kneeling bus services
Services such as b.line services starting with 25, 26 or 27 and the 858 North Shore Hospital service use easily accessible buses that kneel on request. These buses can expel air out of their suspension on one side to reduce the step height. To get a bus to kneel, simply ask the bus driver.
Wheelchair accessible bus services
Services such as the 283 Hospitals bus, 380 Airporter, 007, Northern Express and all LINK Services are operated by Wheelchair Accessible Buses which are specially designed to accommodate wheelchairs. Please check with your service operator to confirm your wheelchair meets size and weight requirements.
On-request audio and braille
Improvements to our bus services are always being made, with recent examples including on-request audio announcements (by pushing the yellow button) and Braille signage at bus stops with Real Time signs. New signage is also being installed with larger icons and fonts for those with visual impairments.
Train accessibility information
All train services welcome passengers accompanied by service dogs or disability assist dogs.
Wheelchair access on the train
All train services are equipped with wheelchair ramps and wheelchairs may be carried at any time. Some types of small battery powered mobility scooters may also be carried in off-peak times.
Mobility scooters and wheelchairs can be carried on the Auckland rail network, subject to the following restrictions:
- Maximum length: 1350mm.
- Maximum width: 650mm.
- Maximum laden weight: 200kg.
These dimensions and weights are necessary to enable safe negotiation of the loading ramp.
The mobility devices described above are deemed to be for disabled passengers and exclude personal motorised mobility devices, such as Segways, which may not be carried on passenger services.
If you require assistance boarding the train or travelling on the train, please ask either the on-board or platform staff.
Station disabled access
Disabled access is not available at Westfield station, please use an alternative nearby station (Sylvia Park, Otahuhu, Middlemore).
Due to station work at Papatoetoe, please board at the southern end of the platform.
Train operator contact details
|Train Operator
|Contact details
|Transdev Auckland Ltd
|09 969 7777
Open Monday to Friday 8.30am to 5.30pm
|Tranz Scenic - Long distance trains
|0800 872467
Ferry accessibility information
Wheelchairs can be taken aboard most ferries, please check with the ferry operator before travelling. If you require assistance boarding the ferry from a suitable waiting point, please contact the ferry operator to arrange this in advance. If you require assistance while travelling on the ferry, please ask the on-board crew.
Ferry operator contact details
|Ferry operator
|Contact details
|Fullers Ferries
|09 367 9111
|360 Discovery
|09 307 8005
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|09 536 4720
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|09 416 6344
|For Waiheke and Great Barrier Island car ferry services
09 300 5900 or 0800 732 5465
Concessionary fares
Concessionary fares are available to passengers who hold one of the following photo ID cards:
- Auckland Transport Total Mobility ID card.
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The concession allows the above card holders to purchase a one way child cash fare at any time.
The ID card must be shown when the ticket is issued and when boarding the bus, train or ferry.
This discount does NOT apply to the City LINK, Inner LINK, NiteRider, Airbus Express buses.


text:
The Sixth International Conference on Cell Therapy for Cardiovascular Disease (IC3D) is a one-and-a-half day comprehensive program dedicated to the evolving field of cell-based therapies for the repair and regeneration of cardiac and vascular disease, as well as related diseases such as diabetes and stroke. This year's conference will focus on commercialization aspects of the field, highlighting the status of molecular, cell, and tissue products in addition to delivery systems.
Now in its 10th year of clinical trials, the application of stem cells in the treatment of cardiovascular diseases has seen many notable successes, as well as identified challenges that await the next round of clinical studies. Leaders in the field will convene to present their work, experiences, observations, and opinions on the benefits and unmet challenges of cell-based therapies.
Sessions will focus on:
Warren Sherman, MD, Course Director, is Director of Cardiac Cell-Based Endovascular Therapies at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital and Columbia University Medical Center. Dr. Sherman is a renowned clinical investigator in the field of myocardial regeneration who pioneered a technique for injecting stem cells into the heart. In Rotterdam in May 2001, he performed the first catheter-based injection of stem cells into the heart of a patient with congestive heart failure due to a previous heart attack. At Columbia University Medical Center, researchers led by Dr. Sherman are using the patient's own myoblasts -- progenitor cells found in muscle -- to repair and replace injure
|Contact: Judy Romero
Cardiovascular Research Foundation


text:
- Publisher: Namco Bandai Games
- Release Date: Feb 22, 2011
- Also On: PlayStation 3
User Score
Mixed or average reviews- based on 13 Ratings
User score distribution:
Positive: 5 out of 13
Mixed: 2 out of 13
Negative: 6 out of 13
Review this game
- User score
- Most active
- By date
- Most helpful
There are no positive user reviews yet.
May 6, 2011Okay combat, some neat spell effects, okay levels, a protection mechanic that works, upgradeable powers, spells and special items, and protracted cutscenes that revel in being overly dramatic (that's a positive in my book), make Knight's Contract utterly unremarkable.
Apr 28, 2011It's got an interesting story, a control setup that's not too hard to get used to (aside from the annoying lock-on mechanic), and the graphics and sound are nice, though the music can get repetitive after a while.
Apr 25, 2011Knights Contract has a cool premise by design but an abysmal AI completely defeats the purpose and chance at having any fun within.


text:
Your nominations for best breakfast eateries in Scunthorpe
Posted: February 10, 2014|
After Wetherspoon's, which runs the Blue Bell pub in Scunthorpe town centre, won a national accolade for the quality of its breakfasts, we gave North Lincolnshire people the opportunity to name their favoured venues.
The results of our Best Breakast survey are now in and here are the top three - in no particular order:
Frankie and Bennys at Glanford Park/Jack Brownsword Way: It was described as offering really nice decor, good food that's really well prepared, first class friendly and efficient service, culminating ijn excellent all-round value for money.
Scalinis, in Ravendale Street, Scunthorpe: Nominated for cooking every meal to order. Our correspondent says: "You can see it being prepared. It is very good food and value. You only have to see all the longtime regulars to know why. We have spoken to people who travel from quite far away who eat there, and I don't think it is the shopping centre that attracts them."
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Man v Food! Which pub serves biggest portions in Scunthorpe?
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Blue Bell pub in Scunthorpe getting new £30k toilets
Sarah's Diner, on Scunthorpe High Street: Nominated for fast, efficient service and for offering a huge choice. Our correspondent said: "You can make combos of all sorts. There's a friendly atmosphere and good, tasty no-nonsense breakfast fare."


text:
2 killed, 10 hurt as bus falls into ravine in San Carlos City
BACOLOD CITY, Philippines— (UPDATE 2) At least two persons were killed and 10 others were wounded Wednesday night when a bus, whose driver insisted on driving with defective headlights, fell into a ravine on the outskirts of San Carlos City in Negros Occidental. Five or six passengers were unaccounted for.
The driver, Teodoro Aburido, died on the spot when the Ceres Liner bus he was piloting plunged into a ravine that was at least 60 meters deep. The bus was headed for San Carlos from Bacolod, and swerved off the road in Sitio Dukog-dukog, Barangay Rizal, in San Carlos.
Chief Insp. Victorino Romanillos, acting chief of the San Carlos police, said they had yet to identify the second fatality.
He said the authorities were still searching for about five to six passengers who remained missing.
The police have yet to determine the real cause of the accident, but passengers reported that the headlights of the bus had gone out at least four times while they were travelling through the foggy road.
They claimed that Aburido continued driving until the bus fell into the ravine.
Police said there were 21 people on board—18 passengers, the driver, an bus inspector and a conductor.
The Ceres bus with body number 5229 left Bacolod past 5 p.m. through Don Salvador Benedicto town.
When it reached Dukog-dukog, the bus fell into a ravine that was at least 60 meters deep.
Romanillos said members of various rescue groups in San Carlos City, and San Carlos policemen immediately went to the scene to rescue the passengers.
Among the 10 passengers who were wounded was PO3 Edsel Villanueva, a member of the Calatrava Police Station.
Romanillos said four of those wounded were taken to two hospitals in San Carlos City but were later transferred to medical facilities in Bacolod.
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text:
Comprehensive, atomic-level characterization of structurally characterized protein-protein interactions: the PICCOLO database
1 Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK
2 Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK
BMC Bioinformatics 2011, 12:313 doi:10.1186/1471-2105-12-313Published: 29 July 2011
Structural studies are increasingly providing huge amounts of information on multi-protein assemblies. Although a complete understanding of cellular processes will be dependent on an explicit characterization of the intermolecular interactions that underlie these assemblies and mediate molecular recognition, these are not well described by standard representations.
Here we present PICCOLO, a comprehensive relational database capturing the details of structurally characterized protein-protein interactions. Interactions are described at the level of interacting pairs of atoms, residues and polypeptide chains, with the physico-chemical nature of the interactions being characterized. Distance and angle terms are used to distinguish 12 different interaction types, including van der Waals contacts, hydrogen bonds and hydrophobic contacts. The explicit aim of PICCOLO is to underpin large-scale analyses of the properties of protein-protein interfaces. This is exemplified by an analysis of residue propensity and interface contact preferences derived from a much larger data set than previously reported. However, PICCOLO also supports detailed inspection of particular systems of interest.
The current PICCOLO database comprises more than 260 million interacting atom pairs from 38,202 protein complexes. A web interface for the database is available at http://www-cryst.bioc.cam.ac.uk/piccolo webcite.