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ASCO 2008: An Update for Nurses
ASCO 2008: An Update for Nurses
Every year, at the American Society for Clinical Oncology annual meeting, physicians present findings from research studies that change or clarify the way we treat patients with cancer. Unfortunately, nurses don't always get this information right away, but often times our many internet-savy patients do. This continuing education module is designed to provide nurses in practice the latest information on select topics presented at ASCO 2008.
ACOSG ZO531: Report on a Multicenter, Phase II Trial for Adjuvant Therapy of Resected Pancreatic Cancer Using Cisplatin, 5-FU, and Alpha-Interferon
Surgery is considered the only curative therapy for pancreatic cancer. However, 50-80% of patients will develop recurrence after surgery. For this reason, patients also receive adjuvant (meaning postoperative) chemotherapy, either with or without radiation therapy. While this therapy improves survival, it only results in a 10-20% 5- year survival. Previous studies have shown that the addition of interferon alpha may make cisplatin chemotherapy work better in making tissues sensitive to radiation (radiosensitizing) and in improving survival.
This study gave all participants 5-FU, cisplatin, and alpha interferon. The study hoped to enroll 93 patients, but was stopped early with 89 participants due to high rates of toxicities. Overall survival (OS) was 69% at 20 months and 58% at 2 years. 96% of patients had a grade 3 or 4 (on a scale of 0-4, 4 being the most severe). The toxicities most commonly seen were anorexia (loss of appetite), dehydration, diarrhea and nausea. These toxicities were significant, but manageable with supportive care.
There are now three studies evaluating the efficacy of cisplatin, 5-FU, alpha interferon, and radiation. These studies include the Virginia Mason study (Picozzi V.J. et al., ACSO Annual Meeting 2003), the CapRI study (Knaebel H.P. et al., BMC Cancer, 2005; presently under analysis), and the present study. Data is available for over 174 patients from these studies, and they have consistently demonstrated a 2-year OS of greater than 50%. The CapRI study is the only randomized trial, and results are pending. It is important to note that the patients in this study were highly selected, and there is the potential for bias regarding patient enrollment.
The greatest problem with this regimen is the toxicity related to treatment, as seen now in multiple studies. The majority of these toxicities were related to anorexia and dehydration. It is unclear what supportive care patients received, such as whether feeding tubes were placed and used, the use of IV fluids, monitoring of patient weight during treatment, and use of pre-albumin levels. Without this information, it is difficult to know if there was adequate supportive care to get patients safely through treatment. The inability to complete treatment was associated with worse outcome and this was likely affected by the high toxicity associated with treatment. However, despite this toxicity and the significant number of patients who could not complete therapy, the outcomes were quite good compared with historical controls. Hence, if the tolerability of this treatment could be improved, such as through better supportive care, outcomes might improve as well.
Bortezomib/dexamethasone versus VAD as Induction Prior to Autologous Stem Cell Transplant (ASCT) in Previously Untreated Multiple Myeloma (MM): Updated Data from IFM 2005/01 Trial
The use of autologous stem cell transplant in treating multiple myeloma patients over 65 years of age has become standard therapy. Traditionally, the VAD chemotherapy regimen was used as first line induction therapy. This study looked at using bortezomib and dexamethasone (BD) as induction therapy, compared with VAD. This was based on the theory that both bortezomib and dexamethasone inhibit different peptides, resulting in a blockade of important cell pathways that are necessary for growth and replication. It is hoped that this interference will lead to greater cell death.
Patients were randomly assigned to one of the following therapies:
BD alone (4 cycles), VAD alone (4 cycles), BD followed by consolidation therapy with 2 cycles of dexamethasone, cyclophosphamide, etoposide, and platinum (DCEP), or VAD followed by 2 cycles of DCEP. 442 patients were evaluated.
BD had superior response rates in low-, intermediate-, and high-risk patients. Patients with high and low levels of beta2 microglobulin and patients with and without deletion of chromosome 13 all benefited from BD therapy. The responses were classified as complete and near complete (8.3% in VAD arm vs. 21.3% in BD arm) and "more than a very good partial response" (18.6% in the VAD arm vs. 46.7% in the BD arm). These patients went on to have stem cell transplants, and the superior response in the BD arm was still present after transplant. The addition of DCEP did not increase response rates. The BD superiority did not translate into improved survival rates at 18 months, but longer follow up is needed.
Side effects varied, with neuropathy and thrombocytopenia being higher in the BD arm and neutropenia and anemia being higher in the VAD arm.
Although this study does suggest great potential for this induction therapy regimen, it is not yet the standard of care. Longer follow-up is needed, and there should ideally be a true improvement in quality of life, overall survival, and/or cost of treatment (with equivalence of effect) prior to accepting this regimen as the standard of care for induction prior to ASCT.
BRCA1 mRNA expression in patients with bladder cancer treated with neoadjuvant cisplatin-based chemotherapy
Improved overall survival has been demonstrated with the use of cisplatin-based chemotherapy given prior to radical cystectomy in patients with locally advanced bladder cancer, as compared to radical cystectomy alone (Lancet, 2003). Although the majority of patients who are planned to undergo radical cystectomy receive cisplatin-based chemotherapy, no tumor or clinical marker currently exists to predict whether they will benefit from this treatment. Avoidance of platinum-based chemotherapy in patients with a decreased likelihood of benefit from these agents would be helpful.
Mutations in the BRCA1 gene (breast cancer susceptibility gene 1) have been associated with both increased risk of development of certain cancers, and resistance to chemotherapy. Overexpression of BRCA1 mRNA has recently been demonstrated to be predictive of in vitro (in the laboratory) sensitivity to cisplatin and docetaxel in metastatic lung, gastric and ovarian cancers. This study evaluates the role of overexpression of BRCA1 mRNA in bladder cancer patients with regard to response to treatment, disease-free survival, and overall survival.
98 patients with varying stages of disease were evaluated. Tumor tissue was tested and BRCA1 mRNA levels were found to be low in 35% of patients, intermediate in 32%, and high in 32%. Response to the chemotherapy was seen in 66% of patients with low or intermediate levels but only 23% of patients with high levels. Disease-free survival (that is, survival without any recurrence) was strongly correlated to the BRCA1 mRNA levels. DFS was 120 months in patients with low BRCA1 mRNA levels, 184 months in those with intermediate levels, and 14 months in those with high levels. Five-year overall survival (that is, survival with or without recurrence) was 63% in patients with low or intermediate BRCA1 mRNA expression, and 23% in those with high levels.
While this study suggests that BRCA1 mRNA levels can be used to predict response to cisplatin therapy, a randomized trial could be indicated to evaluate this as well as the response to taxane therapy for those with high expression levels.
Cancer-related fatigue interferes with activities of daily living among 753 patients receiving chemotherapy: A URCC CCOP study
Cancer-related fatigue is unfortunately a very common problem with few to no effective solutions. This study looked to evaluate rates of fatigue and how they interfere with activities of daily living (ADLs) (such as work, bathing, dressing, walking) in 700 patients. Assessment of fatigue was performed one week after the first cycle of chemotherapy and one week after the second cycle.
Researchers found that fatigue was present as soon as 1 week after the first chemotherapy cycle (this was the first time point they assessed). Fatigue interfered significantly with many essential ADLs, and most significantly with walking, completing household chores, and running errands. Of the 11 ADLs researchers asked about, 9 were reported to be affected after the first cycle and 10 after the second cycle of chemotherapy.
Although this study demonstrated that fatigue affects ADLs, there was no baseline assessment of fatigue, and the testing period was quite short. The study adds to the body of knowledge regarding fatigue, but does not offer any interventions for relief.
CONKO-001: Final Results of the Randomized, Prospective, Multicenter Phase III Trial of Adjuvant Chemotherapy with Gemcitabine vs. Observation in Patients with Resected Pancreatic Cancer (PC)
This study has previously reported (Oettle H., et al. JAMA 2007) that the use of post-operative gemcitabine in patients with pancreatic cancer significantly delays the development of recurrent disease after complete resection and is generally well tolerated. This presentation is an update of their previously published results.
354 patients were randomly assigned to receive gemcitabine for 6 months after surgical resection or no therapy after surgical resection. Median overall survival was 22.8 months in the chemotherapy arm (arm A) versus 20.2 months in the supportive care arm (Arm B). The survival difference increased over time:
1 Year
2 Year
3 Year
5 Year
Arm A
Arm B
The findings from this study suggest that gemcitabine is safe and effective in the postoperative setting, and its use should be considered. It is important to keep in mind that the patient population enrolled in this study was a highly selected one, in that the postoperative CA 19-9 levels had to be less than 2.5 times the upper limit of normal. This is a requirement that might rule out many postoperative pancreatic cancer patients.
The optimal postoperative management regimen continues to be studied by several groups. The use of combined regimens and whether or not to include radiation therapy are among the treatments being studied. Hopefully these studies will help determine the optimal regimen for postoperative use.
Effect of intravenous calcium and magnesium (IV CaMg) on oxaliplatin-induced sensory neurotoxicity (sNT) in adjuvant colon cancer: Results of the phase III placebo-controlled, double blind NCCTG trial N04C7
The addition of oxaliplatin to the arsenal of therapies for GI cancers has had a profound effect on survival, but not without additional side effects. In particular, neuropathy has resulted in delays and reduction in doses and more importantly, resulted in poor quality of life for those affected. Researchers have determined that oxaliplatin-related neuropathy resembles muscle abnormalities such as mytonia and tetany, which are thought to be related to a decrease in calcium (Ca) and magnesium (Mg) levels. Small studies used Ca and Mg intravenous infusions to prevent oxaliplatin-induced neuropathy with some success. This presentation reviewed a large phase III study in which Ca and Mg infusions were used in the hopes of preventing this side effect.
The study was ultimately closed early, with 102 of a planned 300 patients being evaluated. The study was closed because another trial suggested that Ca and Mg infusions may decrease the efficacy of oxaliplatin. Participants received either Ca/Mg infusion or placebo along with standard chemotherapy. Patients were assessed using an NCI scale, a scale specific to oxaliplatin related neuropathy and a quality of life scale. The infusion group performed better on both side effect scales. Percent of participants with grade 2 or higher neuropathy on the NCI scale: 22% for Ca/Mg group versus 41% for the placebo group. On the oxaliplatin specific scale, grade 2 or higher neuropathy was seen in 28% for Ca/Mg group versus 51% for the placebo group. As for quality of life ratings, there was a trend towards improved swallowing and muscle cramps in the Ca/Mg group, but these differences were not yet statistically significant, which may be due to the smaller-than-expected sample size.
The suggestion that the addition of Ca/Mg may affect response rates by the CONCEPT study has dampened the results of this study, but there were some questions of how response was evaluated in the study. Further studies are needed to clarify this issue as this study has clearly shown that Ca/Mg infusions can provide benefit and could possibly lead to fewer dose reductions.
Effect of paroxetine on depression and insomnia in 547 fatigued cancer patients undergoing chemotherapy
Depression and insomnia are two common issues in people with cancer. Studies have found that approximately 30% of people with cancer report insomnia and they are 2.5 times as likely to have insomnia compared with the general population. This study was carried out in order to determine the effectiveness of paroxetine in treatment of both depression and insomnia in patients undergoing treatment for cancer.
Patients were enrolled prior to beginning cancer treatment, and patient depression, insomnia, and fatigue levels were assessed at the time of each of the first four chemotherapy sessions. Following the second cycle of chemotherapy, 547 patients who reported cancer-related fatigue were randomized to receive paroxetine, 20 mg orally daily, versus placebo.
Patients randomized to paroxetine experienced significantly decreased rates of depression (p < 0.05) when compared to the control arm. A trend towards improvement in insomnia was noted in patients randomized to paroxetine, but this was not statistically significant. No impact on fatigue was seen in patients randomized to paroxetine versus those taking placebo. The researchers concluded that although the paroxetine improved depression, it did not improve insomnia or fatigue. This study is a well-designed trial that raises awareness of the need to consider insomnia as a separate entity from, and not an entity caused by, depression in cancer patients.
Effects of aerobic exercise training on physical performance during myeloablative therapy
The benefits of exercise for people undergoing cancer therapy have been shown in previous studies. These include improvements in lung and heart function, increased strength and improvements in fatigue levels. The purpose of this study was to evaluate effects of anaerobic exercise training on physical performance of patients with hematologic malignancies or solid tumors during myeloablative therapy or high-dose chemotherapy followed by autologous peripheral blood stem cell transplant.
The questions to be answered by the authors were:
1) Is exercise feasible in this group of patients?
2) What happens to physical performance in these patients if they do exercise?
The study included 85 participants undergoing high dose chemotherapy, who were randomly assigned to a 30 minute a day, 5 days a week exercise regimen or no exercise regimen. Both groups completed daily questionnaires on side effects and quality of life. Exercise was held when platelets or hemoglobin were low, for infection, fever or if the patient was in the ICU.
The primary endpoint was change in physical performance between the beginning and end of treatment, measured in Watts (W). There was a significant increase in physical performance in the exercise group (8.96 +/-24 W) and a decrease in the control group (-7.24 +/- 20 W). The exercise group had improvement in lung function and an increase in their physical functioning score. Patients tended to be fitter and feel better at discharge if they performed exercise.
The exercise regimen during myeloablative therapy appears to be achievable, effective, and safe, and may help to preserve physical function in these patients. Ultimately, this can reduce the risk for limitations and disabilities in patients later in life.
Epidemiology study of never-smokers with non-small cell lung cancer (NSCLC): High percentages of Asian and Hispanic female never-smokers and the significance of Asian ethnicity
Non-small cell lung cancer (NSCLC) remains the number one cause of cancer death in both men and women in the United States. The greatly increased risk of NSCLC development in tobacco users has been well recognized for several decades. More recently, a sharp rise has been seen in NSCLC among never smokers and this cancer has been found to be biologically different from that of a NSCLC in a current of former smoker. Common features of never-smokers with NSCLC have been identified, including East Asian ethnicity, female sex, adenocarcinoma (specifically bronchoalveolar) pathology, and an increased likelihood of EGFR mutations, which may result in different therapy choices. This study attempted to increase the understanding of the epidemiology (the occurrence and distribution) of NSCLC in never smokers and to look at the affect of ethnicity on prognosis.
Utilizing a southern California database that included smoking status, 2240 never smokers were identified with a NSCLC diagnosis (and compared with 22964 current and former smokers). Never smokers had significantly improved survival when compared with smokers. Never smokers responded better to chemotherapy, with an 8 month median survival in never-smokers versus 6 month median survival in smokers with metastatic disease receiving chemotherapy. Response to radiation therapy also appears to be better.
When the never smokers (NS) were compared to the smokers (SK), the NS group contained more females, their tumors were more likely to be adenocarcinoma and more specifically, bronchoaveolar. When looking at ethnicity, 13% of Caucasian women were NS, 45% of Asian women were NS, and 25% of Hispanic women were NS. Of women born in North America, 11% of women born in Canada and 12% of women born in the United States with NSCLC were never-smokers. Thirty percent of women born in Mexico with NSCLC were never smokers. Of women born in Asian countries with NSCLC, 53% of Philippine women, 64% of Vietnamese women, 17% of Japanese women, and 61% of Chinese women were never-smokers.
Being of Asian ethnicity was a favorable prognostic sign for both NSs and SKs. Other groups have demonstrated improved responses among Asian women to certain therapies. While the information from this study is interesting, actual treatments were not considered and the population was limited to one geographic area. It is unclear what is driving the rise in these ethnic groups. Further studies must look at exposures and genetics as possible causes and evaluate how ethnic factors play into treatment decisions.
Evaluation of chromosome 17 (Chr-17) polysomy in Her2 FISH-negative metastatic breast cancer (MBC) patients enrolled in a randomized phase III study of paclitaxel and lapatinib
Researchers believe that having multiple copies of a cromosome (i.e. 3 or more, a condition known as polysomy), specifically of chromosome 17, may result in higher expression of Her-2, thus leading to a greater response when treated with Her-2 inhibitors, such as lapatinib. This study evaluated whether women with Her-2 negative tumors who had chromosome 17 polysomy would derive a benefit from lapatinib.
Unfortunately, no statistically significant difference in progression-free survival was seen between the various groups. The authors conclude that women with Her-2 negative tumors will not derive any benefit from Her-2 inhibitors, regardless of the status of chromosome 17.
Intermittent oxaliplatin (oxali) administration and time-to-treatment failure (TTF) in metastatic colorectal cancer (mCRC): Final results of the phase III CONCEPT trial
The CONCEPT trial (Combined Oxaliplatin Neuropathy Prevention Trial) was designed to study patients with mCRC receiving Oxaliplatin/ Bevacizumab as 1 st line treatment, and to evaluate whether giving oxaliplatin intermittently (IO) in a regimen of FOLFOX/Bevicizumab would reduce cumulative neurotoxicity, and therefore allow patients to stay on treatment longer than those receiving a conventional Oxali schedule (CO). The authors also explored the impact of calcium and magnesium (CaMg) administration on neurotoxicity.
Patients were randomly assigned to receive either standard FOLFOX given every 2 weeks (CO) or FOLFOX alternating with 5-FU/Leucovorin and bevacizumab (IO group). Each group was further divided so that half received calcium (Ca) and magnesium (Mg) infusions and half received a placebo in an attempt to decrease neurotoxicity.
Many studies do a review of the results partway through, so that the study can be stopped if one group is doing much better. This study was stopped early because the investigators felt that the groups receiving Ca/Mg were having poorer responses to therapy. Critics have pointed out that the evaluation of response was not confirmed and was done by the investigator, who may have been biased. While the study has been stopped, further analysis continues into the responses.
Despite stopping early and having a smaller-than-planned sample size; the group receiving intermittent (IO) oxaliplatin did have better responses to therapy. Progression-free survival (that is, survival with no recurrence) was 12 months in the IO group versus 7.3 months in the CO group. In addition, the incidence of severe neurotoxicity was improved, 24% (CO) versus 10% (IO). And this toxicity also corresponded with a need for dose reductions, leading to more dose reductions in the CO group.
Despite the early termination of the study, the IO regimen appears to achieve the goal of keeping patients on therapy longer, and the Ca/Mg infusions appear to reduce neurotoxicity, also leading to better treatment adherence. Further study is needed to determine if the study was stopped prematurely, so stay tuned.
FLEX: A randomized,multicenter, phase III study of cetuximab in combination with cisplatin/ vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)
Epidermal growth factor (EGFR) is over expressed in 80% of lung cancers. Cetuximab is a monoclonal antibody that interferes with EGFR. A previous randomized phase II FLEX (First-Line Treatment for Patients with EGFR-expressing Advanced NSCLC) trial compared cisplatin and vinorelbine (CV) to cisplatin, vinorelbine, and cetuximab (CV+C) in patients with advanced NSCLC. Forty-three patients were randomized to each arm. Improvement in outcomes were seen with the addition of cetuximab; tumor response was improved from 28% to 35% with addition of cetuximab, progression-free survival was improved from 4.6 months to 5 months, and overall survival was improved from 7.3 to 8.3 months (Rosell, 2008).
Data from the FLEX phase II trial prompted the design of the FLEX phase III trial a larger trial utilizing the same therapies as FLEX II in more patients to evaluate survival benefit.
1125 patients participated in the study, with 94% having stage IV disease. Median overall survival* (OS) was 11.3 months in the CV + C arm, versus 10.1 months in the CV arm. One-year OS was 47% and 42% in the CV + C arm versus CV arm, respectively, which was statistically significant. As far as variation in side effects in the two groups, as expected, 10% patients receiving cetuximab developed rash, while virtually no one in the CV arm developed rash. Neutropenic fever was seen in 22% of those receiving CV+C versus 15% in the CV arm.
The authors point out the survival benefit, which is quite small, as reason to change standard therapy, but one must consider the cost of adding cetuximab to all regimens. Patients with adenocarcinoma appeared to derive the most benefit from the addition of cetuximab. Further research may determine a way to better classify which patients will derive the most benefit. In the meantime, this trial demonstrates a modest but real survival advantage for patients with advanced NSCLC treated with cetuximab added to conventional chemotherapy versus chemotherapy alone. This data is interesting and supports findings in head and neck and colorectal cancer that cetuximab is effective and safe when utilized concurrently with conventional chemotherapy. These findings are clinically important, and are an important contribution to the literature regarding treatment of patients with NSCLC.
* The median is the "middle of the pack", where half of the patients have had more years since treatment and half have had less. For instance, if the patients were 2, 4, 6, 10.8, 12, 12 and 14 years since treatment, 10.8 is the mid point, or the median. It is different from the mean, which would be the average time since treatment.
KRAS Status and Efficacy in the First –Line Treatment of Patients with Metastatic Colorectal Cancer (mCRC) Treated with FOLFIRI with or without Cetuximab: The Crystal Experience
Cetuximab is a targeted therapy agent that blocks epidermal growth factor receptor (EGFR) and that is used in the treatment of colon cancers. EGFR has several targets, including one called k-ras. K-ras is a protein that is activated when bound to GTP. GTP can then convert to GDP, which turns off k-ras. However, if k-ras is mutated, it can remain constantly active. So, if the k-ras is mutated, it no longer relies on EGFR to work, and therefore may be less likely to be affected by a therapy that blocks EGFR (i.e. cetuximab). Researchers refer to unmutated k-ras as "wild type", and feel that this wild type may be more responsive to cetuximab.
The CRYSTAL trial (Van Custem E., et al., ASCO Annual Meeting , 2007) was a large, randomized, phase III trial which investigated the use of FOLFIRI (Arm A) versus FOLFIRI plus cetuximab (Arm B) as first-line treatment in EGFR-expressing advanced colorectal cancers. Results demonstrated an increase in both response rate (RR), median progression-free survival (PFS), and curative surgery rates in the arm with cetuximab. This presentation was an analysis of patients in whom k-ras status was available (about half of the original study participants).
Mutated k-ras (MT) was present in 35.6% of these patients and wild type (WT) in 64.4%. Patients with WT k-ras improved with the addition of cetuximab: median* survival was 9.9 months for patients in arm B versus 8.7 months for patients in arm A. Outcomes for patients with mutant k-ras were not affected by the addition of cetuximab: median survival was 7.6 months for arm B versus 8.1 months for arm A.
Response to FOLFIRI was similar for patients with WT and mutant k-ras. The duration of treatment was longer in patients with WT k-ras, likely reflecting their better outcome and longer survival. There was no difference in toxicity seen between patients with WT and those with mutant k-ras. In the original CRYSTAL study, there was more grade 3 or greater toxicity in the cetuximab arm. This held true for patients with WT and mutant k-ras in the present study (both groups had more grade 3 or higher toxicity with cetuximab).
Based on these data, k-ras status should be assayed in patients who are candidates for cetuximab or panitumumab therapy, as it appears that only those with WT k-ras will benefit. This will spare k-ras mutant patients unnecessary toxicity. It is also important to tell patients with k-ras mutation that traditional chemotherapies remain effective. Further development of an easily accessible, reliable assay to determine k-ras status is still necessary to implement these findings on a wide-spread basis.
* The median is the "middle of the pack", where half of the patients have had more years since treatment and half have less. For instance, if the patients were 2, 4, 6, 10.8, 12, 12 and 14 years since treatment, 10.8 is the mid point, or the median. It is different from the mean, which would be the average time since treatment.
A phase II randomized, placebo-controlled, double blind trial of a eugeroic agent in 642 cancer patients reporting fatigue during chemotherapy: A URCC CCOP study
Cancer-related fatigue (CRF) is one of the most common side effects of cancer and its treatment, and has been shown to affect nearly 70-100% of cancer patients in previous studies. This study evaluated the effect of modafanil, an agent used in the treatment of narcolepsy, on cancer related fatigue.
642 participants were randomly assigned to receive modafanil or placebo from the second cycle of chemotherapy through the fourth. The drug had a positive effect on fatigue, but only for those patients who rated their fatigue as severe. The group receiving modafanil also reported less sleepiness.
Unfortunately, the researchers did not report on the side effects of the drug, so it is difficult to know how well tolerated it was among the participants. The scale used to measure fatigue may not have been the best choice. More data may have been gained from evaluating functional status or time spent sleeping during the day. Although some questions remained unanswered, this data may help to further study this or other drugs in the treatment of fatigue.
A phase III randomized study comparing the effects of oxandrolone (Ox) and megestrol acetate (Meg) on lean body mass (LBM), weight (wt) and quality of life (QOL) in patients with solid tumors and weight loss receiving chemotherapy
A study by DeWys, et. al. in 1980 showed that unintentional weight loss in cancer patients is a significant problem and is a poor prognostic factor. It is associated with decreased survival and QOL, and increased toxicity to cancer treatment. The weight loss in cancer patients is disproportionately seen as a loss of muscle mass rather than fat, which may be a reason for the negative effects mentioned above. Common drugs such as megestrol acetate (or Megace) and corticosteroids (such as dexamethasone and prednisone) have been standardly used to reduce unintentional weight loss, and can actually help patients gain weight. Oxandrolone (Oxandrin, Ox) is an oral anabolic steroid, which has a high anabolic-to-androgenic ratio. For this reason, it is proposed that this drug promotes weight gain by promoting muscle regrowth and increasing LBM. Ox has been used for a variety of medical disorders causing involuntary weight loss, and has often been used by body builders to build muscle. The purpose of this phase III study was to compare the effects of Ox to Meg (a current standard) on LBM and weight of patients.
155 cancer patients who had experienced a 3% or greater loss of body weight were randomly assigned to receive Ox twice a day or Megace daily while undergoing chemotherapy. 60% of those enrolled had advanced disease. There was a significant improvement in weight and change in fat mass in the Megace group. The Ox group actually lost weight and fat mass. There was a 50% study dropout rate, which was much higher in the Ox arm (69%) versus 39% in the Megace arm.
It is unclear whether the advanced stage of disease played a role in the patients on Ox losing weight. The authors neglected to discuss why the drop out rate was so high, which could be related to toxicity. The researchers are now looking to perform a trial comparing megace to Ox given with megace and it will be useful to see if the combination improves weight outcomes.
A Phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: Survival results of NSABP Protocol C-07
Previous studies have shown a benefit to adding oxaliplatin to the standard 5-FU and leucovorin in adjuvant therapy for stage II or III colon cancer. This report is an update of the results of a phase III study comparing 5-FU/LV (FULV) with 5-FU/LV and oxaliplatin (FLOX) in stage II and III colon tumors.
The study had 2,409 participants randomized to the two regimens. 29% of the participants had stage II disease. At the 3-year update, the difference in disease-free survival was reported as 4.6% (superior in FLOX arm). At this 5-year update, the disease-free survival advantage had increased to a 5.2% advantage in the FLOX arm. However, these differences were not statistically significant. Nonetheless, the authors feel that longer follow up may result in a statistically significant difference. Interestingly, when stage II (node negative) patients were teased out, no benefit was seen for them.
This study could result in a change in the standard of care for adjuvant therapy, but longer follow up is necessary to determine if the benefits seen are significant. The addition of oxaliplatin is not without consequence, as it can cause significant neurotoxicity, affecting quality of life.
Prophylaxis of recurrent chemotherapy-induced oral mucositis: A phase II multicenter, randomized, placebo-controlled trial of recombinant human intestinal trefoil factor (rhITF)
Oral mucositis is a common, debilitating symptom affecting many patients on high-dose chemotherapy. It is an inflammation of the mucous membranes of the mouth, and can often range from erythema and sores to severe ulcerations. It can be quite painful, and often prevents patients from eating, drinking, or talking for long periods of time.
Intestinal Trefoil Factor (ITF), is a protein found mostly on mucosal surfaces throughout the gastrointestinal tract. ITF has been shown to promote mucosal protection, repair, and restitution. Therefore, it is hypothesized that therapy with recombinant human ITF (rhITF) can alleviate damage to the mucosa of the oral cavity and lessen the effects of oral mucositis. This study randomly assigned 99 patients receiving 5-FU chemotherapy, who had mucositis with their first cycle of chemotherapy, to receive placebo, low dose ITF, or high dose ITF (in the form of an oral spray).
The results:
Low Dose
High Dose
# of patients with grade 2 or greater mucositis
No serious side effects were reported. These results are quite promising, but this is a very small study and further study must be done on larger groups. It will also be interesting to study this drug in other patient populations, particularly stem cell transplants, where oral mucositis is quite severe.
RAD001 versus placebo in patients with metastatic renal cell carcinoma (RCC) after progression on VEGFr-TKI therapy: Results from a randomized, double-blind, multicenter phase III study
RAD001 (Everolimus) is an oral targeted therapy medication that inhibits mTOR, which regulates cell proliferation (growth) and angiogenesis (development of blood vessels). This phase III study compares RAD001 to placebo in patients with metastatic renal cell cancer that has progressed with either sorafenib or sutent.
Many studies perform "interim analyses", where they stop the study partway through, evaluate the results, and stop the study if one arm appears to be superior. This study was stopped after a second analysis found the RAD001 arm to be superior. This allows those patients receiving placebo to receive the therapy as well.
The median progression-free survival was 4.0 months in the RAD001 arm versus 1.9 months in the placebo arm. Benefit was seen in patients classified as favorable risk, intermediate risk, and poor risk. 60% of those receiving RAD001 achieved stable disease, versus 30% on placebo.
Toxicities reported include stomatitis, anemia, and aesthesia. Rarely, pneumonitis, hypercholesterolemia and hyperglycemia were seen in the RAD001 arm.
The benefit of everolimus over placebo is clear from this study, and the authors' conclusion that everolimus should be a standard of care in this setting seems valid, particularly given the fact that no other agent has been demonstrated to be as efficacious to date. Having said this, with the recent advent of targeted agents available to treat metastatic RCC, the timing and sequence with which they will be ultimately used to achieve the best outcomes is undetermined as of yet. Further studies may look at combining therapies or comparing sorafenib/sutent to everolimus to better clarify how to best utilize these therapies.
Radiotherapy versus carboplatin for Stage I seminoma: Updated analysis of the MRC/EORTC randomized trial (ISRCTN27163214)
Seminoma (the most common type of testicular cancer) has traditionally been treated with orchiectomy followed by radiation therapy. Follow-up of these patients found that the radiation therapy resulted in higher risk of mortality, secondary cancers and cardiac issues. Seminomas are known to be quite sensitive to platinum chemotherapy agents. Therefore, this study compared 1 cycle of carboplatin to radiation therapy in stage I seminomas following orchiectomy.
1477 patients were randomly assigned to receive radiation or carboplatin after surgery. This report is based on 6.5 years follow up. There was no significant difference in recurrence-free survival between the groups. There was, however, a significant difference in the rate of 2 nd primary germ cell tumors (GCT). There were 2 (0.3%) cases in the carboplatin group (C) and 15 (1.7%) in the radiation therapy (RT) group.
As for side effects, patients were scored based on percentage of patients able to work at 4 weeks and 12 weeks. There was a significant difference at week 4 between C and RT, with 19% of carboplatin patients unable to do normal work vs. 38% unable to in the radiation group. However, this difference was not present at 12 weeks, at which time the majority of patients in both arms were able to function normally. There was increased grade 2 and 3 thrombocytopenia in the C group compared to the RT group. These results tell us that carboplatin is an effective alternative to radiation therapy for stage I seminomas and should be considered in this population. Longer follow up will look further at secondary cancers and cardiac problems, which may be possible in either group.
Randomised, double-blind, placebo controlled, phase III study of bevacizumab (BV) with docetaxel (D) or docetaxel with placebo (PL) as first line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO
Bevacizumab is a monoclonal antibody that targets VEGF, which allows it to inhibit angiogenesis (growth of blood vessels). A previous study demonstrated that combining bevacizumab with paclitaxel resulted in improved response rate and progression-free survival in metastatic breast cancer. This study was conducted in Europe, where docetaxel is used more frequently than paclitaxel, and looked to combine bevacizumab with docetaxel.
736 participants with metastatic breast cancer were randomized to receive docetaxel + placebo (P), docetaxel + low dose bevacizumab (LD) or docetaxel + high dose bevacizumab (HD). Statistically significant advantages in progression-free survival (PFS) were seen in both bevacizumab arms. Median* PFS in the P arm was 8 months, 8.7 months for the LD arm, and 8.8 months for the HD arm. The percentage of patients who achieved at least a partial response were 44% (P), 55% (LD) and 63% (HD). Survival was not reported, as the median follow up is only 10 months, and more mature data is needed to evaluate survival. Limited toxicity was seen, according to the authors.
The PFS benefit was small in this trial, compared with the trial of paclitaxel and bevacizumab, which saw a greater benefit (5.9 versus 11.8 months). In that trial, paclitaxel was given weekly, which may account for the improvement in PFS. Ongoing studies (RIBBON trial) will further investigate adding antiangiogenesis agents to the treatment options in metastatic breast cancer.
* The median is the "middle of the pack", where half of the patients have had more years since treatment and half have less. For instance, if the patients were 2, 4, 6, 10.8, 12, 12 and 14 years since treatment, 10.8 is the mid point, or the median. It is different from the mean, which would be the average time since treatment.
Randomized Phase III Study of Capecitabine, Oxaliplatin, and Bevacizumab with or without Cetuximab in Advanced Colorectal Cancer (ACC), the CAIRO2 Study of the Dutch Colorectal Cancer Group (DCCG)
This study compared patients with advanced colorectal cancers treated with capcitabine, oxaliplatin and bevacizumab (COB) versus COB + cetuximab. Bevacizumab inhibits the vascular endothelial growth factor (VEGF) receptor, and cetuximab inhibits EGFR. Researchers theorized that combining the two targeted therapies might result in better outcomes.
This unfortunately did not prove to be true. The addition of cetuximab had no effect on overall survival, and actually resulted in worse progression-free survival. The rates of toxicities were higher with the addition of cetuximab. There is some suggestion that there could be a benefit for carefully selected patients. This study highlights the fact that newer targeted therapies are not without toxicities, and combining them may not always be possible.
A Randomized Phase III Study of Gemcitabine in Combination with Radiation Therapy Versus Gemcitabine Alone in Patients with Localized, Unresectable Pancreatic Cancer: E4201
Prior studies of gemcitabine with radiation therapy in pancreatic cancer have concluded that the drug adds toxicity, with little, if any benefit. But, gemcitabine if known to make tissues more sensitive to radiation (called radiosensitization). This study was designed to further study the role of radiation with gemcitabine in unresectable pancreatic cancer.
The study was stopped early due to poor accrual. 71 patients (out of a planned 316) were randomly assigned to receive gemcitabine (G) or G + radiation therapy (GRT). As previously reported, patients with grade 4 (out of 0-4, 4 being most severe) toxicity was much greater in the GRT arm (41.2%), compared to the G arm (5.7%). Overall toxicity was similar, however. There was a small difference in overall survival, 9.2 months for G and 11 months for GRT.
Overall, it appears that radiation prolonged survival, but ultimately most patients still die, based on the overall survival over time that was presented by the authors. Weight loss, QOL, and toxicity were recorded but not reported at this time. Aggressive supportive care is essential, and we await reports of toxicity. With aggressive supportive care, it may be possible to escalate the dose of chemotherapy or radiation used in order to improve outcomes. Unfortunately, after nearly three decades of research, the role of radiation in pancreatic cancer is still not clear at present. These results do appear to affirm that radiation therapy and gemcitabine are more effective than gemcitabine alone, but due to the poor accrual, a larger study is still needed.
A randomized phase III trial of four cisplatin (CIS)- containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: A Gynecologic Oncology Group (GOG) study
Several studies have demonstrated varying degrees of benefit to adding a second chemotherapy to cisplatin when treating advanced cervical cancer. This GOG sponsored study compared 4 potential regimens looking to identify the optimal regimen. Participants were randomized to receive cisplatin given in combination with paclitaxel (P) (which is standard therapy), vinorelbine (V), gemcitabine (G) or topotecan (T). Many studies will perform a data analysis at pre-specified time points during the study and close early if one arm appears superior. In this study, interim analysis found that no arm was superior to the already standard P arm.
Tumor response rates were not significantly different across the four arms. Rates of complete response were 29.1%, 25.9%, 22.3%, and 23.4% for PC, VC, GC, and TC, respectively. No significant overall survival benefit was seen in any arm, nor was there any significant difference in quality of life scores. Toxicities were also similar.
The authors conclude paclitaxel/ cisplatin should remain the doublet of choice in the treatment of advanced or recurrent cervical cancer. An upcoming trial plans to add bevacizumab (an antiangiogenic agent) to the regimen, which will hopefully provide additional benefit as this disease remains very difficult to treat with current therapies.
Randomized Trial of Standard Versus Higher Dose Prophylactic Cranial Irradiation (PCI) in Limited Stage Small Cell Lung Cancer (SCLC) Complete Responders (CR): Primary End Point Analysis (PCI99-01, EORTC 22003-08004, RTOG 0212)
The use of prophylactic cranial irradiation (PCI) in patients with limited stage small cell lung cancer (SCLC) has been shown to provide an overall survival benefit (3-year overall survival of 20.7% with PCI versus 15.3% without) in a large meta-analysis (a study combining the results of several studies) by decreasing the risk of developing brain metastasis. There were a variety of doses and fractionation schemes used in the above mentioned meta-analysis. When the total dose was examined, it appeared that there was a trend towards decreased brain metastasis with higher doses of PCI. This study looked to compare the standard PCI dose to a higher dose.
Participants (n=720) had limited stage small cell lung cancer and were randomly assigned to receive standard dose PCI (SD) or a higher dose, twice-a-day regimen (HD). Toxicities were similar in the two arms. There was no statistically significant difference in the rates of brain metastases between the groups. For unknown reasons, there were lower rates of chest recurrence in the HD group and a decrease in survival in the HD group. For now, standard dose PCI should remain the standard of care.
Relation between perceived cognitive function and neuropsychological performance in survivors of breast and colorectal cancer
"Chemobrain" or "chemofog" was originally described by the female breast cancer population, and refers to symptoms of decreased cognitive acuity described by patients. Often, these symptoms include problems with linear thought and multi-tasking. Studies have found that these symptoms can persist for years after therapy. Other studies have found that patients' self-reported cognitive problems do not match up with how they score on formal cognitive testing. Researchers have suggested that patients may experience a "disorder of insight", or an inability to see how well they actually do function. This study looked to evaluate perceived cognitive function with function based on formal cognitive testing in patients with colorectal and breast cancer.
428 patients were assessed in the study. Overall, 15% of patients reported major perceived cognitive impairment (12% of colorectal patients, and 33% of breast cancer patients). Over the four assessments performed for colorectal cancer patients, perceived cognitive impairment was approximately constant at baseline, 6 months, and 12 months, but appeared to decrease somewhat at 24 months. Formal testing deficit was identified in 22% of patients (22% of colorectal patients, and 14% of breast cancer patients). Interestingly, 31% of colorectal patients had deficits on formal testing at baseline. This improved to 10% at 24 months after treatment.
Perceived poor cognitive function was more closely associated with fatigue, quality of life, and depression than with deficits on formal testing. Patients who received chemotherapy perceived greater impairment, worse quality of life, and worse fatigue, but demonstrated no significant difference on formal testing from those who did not receive chemotherapy.
Correlation between perceived cognitive function and actual NP varied according to diagnosis and gender:
- Among colorectal cancer patients, 71% reported normal perceived function and performed normally on formal testing. This was the case for 51% of breast cancer patients.
- Among colorectal cancer patients, 7% reported impaired function, but performed normally on formal testing. This was the case for 35% of breast cancer patients.
Overall, female patients were more likely to report impairment in the setting of normal formal testing, while male patients were more likely to report normal function in the setting of deficits on formal testing.
While these results appear interesting, there are a few concerns. The formal testing used was not designed for this population and is known to be a poor test for multi-tasking", which is a common complaint in this population. The study evaluated colorectal cancer patients over a period of time, but breast cancer patients only once. The presence of anxiety early on in the diagnosis and treatment process may have a significant affect, but was not tested.
This study demonstrates significant cognitive impairment reported by a high percentage of patients undergoing cancer treatment. The authors demonstrate that this impairment is often not detectable on classical or computer based formal testing. This finding does not decrease the importance or validity of perceived cognitive impairment, however. As the authors point out, both perceived cognitive deficit and objective deficit on formal testing are extremely important, and should be considered as separate but equally important contributions to a patient's quality of life after cancer.
SO124: A Randomized Phase III Trial Comparing Irinotecan/Cisplatin (IP) with Etoposide/Cisplatin (EP) in Patients (pts) with Previously Untreated Extensive Stage Small Cell Lung Cancer (E-SCLC)
The combination of etoposide and cisplatin (EP) is the most widely used chemotherapy regimen for small cell lung cancer. Two large studies looked at using irinotecan and cisplatin (IP), but had conflicting results. The first trial was conducted in Japan and found a significant improvement in overall survival with IP. The follow-up study was conducted in North America and Australia and failed to show a benefit to the newer regimen. It is not clear if the different outcomes were due to ethnic differences in the metabolism of irinotecan. The current study looked at the comparison of EP to IP again to try to determine the best regimen.
645 patients with extensive stage small cell lung cancer participated in the study. The EP arm experienced more neutropenia and thrombocytopenia, while the IP arm experienced more diarrhea. There were no differences seen in overall survival, progression free survival or response rates between the two groups.
This is now the second clinical trial that has failed to demonstrate a survival benefit with IP therapy versus EP therapy in patients with extensive stage SCLC. The authors point out that genetic variability may be responsible for the discrepancy between the two studies. Another potential confounder is cigarette smoking. There have been some data to suggest that smoking affects the metabolism of irinotecan. Unfortunately, smoking status was not recorded in the present study. However, it is also certainly possible, as the authors point out, that the results from the JP511 study were incorrect because it had been stopped early due to toxicities. Nonetheless, from the combined results of the two American trials, it is clear that EP remains the standard of care for extensive stage SCLC.


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Seen a scammer? Been caught out? Let the world know so they don't get burned. Add information if you see one that's already been logged - scammers move quickly and change details often to avoid detection. Details you log here will be in major search engines within an hour or two.Please Like, Share, Tweet etc. to spread the word.
|Scam Reporter
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Manchester, Manchester, United Kingdom
2019-11-11 07:19:12
Classified Ads Scam
| Paypal Scam via Gumtree
Scammer and completely wasted my time.

subset: commoncrawl


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I've been having a bunch of fun making Instagram videos of late. I would say "quick" Instagram videos, but I don't always turn them around as fast as I'd like. After the GoPro Mountain Games in Vail I had a bunch of footage after competing in three different events. We started the day paddling down Gore Creek. I managed to get a video of that published shortly after the weekend, but not the videos of the Bad Ass Dash obstacle course or the XC Mountain Bike race. Finally, those are done and if you didn't catch them on Instagram, I've compiled the three into a YouTube video here:» Full Story »
GoPro Mtn Games 2014
Vail, Colorado, United States
Posted by Cameron on 25 August 2014
Post Fire Kayaking – Soot Water
Poudre River, Colorado, United States
Posted by Cameron on 1 August 2012
Kayak and outdoor enthusiast Christoper Wiegend and I hit the Poudre River in a tandem Jackson Kayak. After the big fire of July 2012 a big rain storm hit. Hopes were the water would be running high and fast but it's the lowest Chris has ever run. The video below was filmed on an iPhone 4 in a LifeProof case and a helmet mounted GoPro camera. Click below for video.» Full Story »
Kayaking & Stand Up Paddleboarding
Roaring Fork Valley, Aspen/Glenwood Springs, Colorado, United States
Posted by Cameron on 25 June 2011
When the snows melt from the slopes and roads in Aspen and turns into water an opportunity to play is created in the rivers. Our adventurous group met up with Charlie MacArthur the founder and owner of the Aspen Kayak and SUP (stand up paddleboarding) Academy. We didn't realize it at the time, though he had that humble air about him, Charlie is a bit of a legend. With years of waterbound experience under his belt, he had a calm, gentle though jovial approach to helping the many of us who had never been kayaking before or for those of us who haven't been in a long while.
Click the title or "Full Story" below to read more and to see the video and photos.» Full Story »
Kayak Fishing
Kachemak Bay, Homer, Alaska, United States
Posted by Cameron on 10 July 2010
After getting off the Kongakut, rest certainly was not an option! We're in Alaska for crying out loud! So, after the 6 hour drive from Fairbanks to Anchorage, we unpacked the car, re-packed the car, loaded kayaks, dropped off rented bear barrels at REI and started the 4 hour drive to Homer.
With the summer solstice having just passed by only the overcast sky really made it seem dark, but we never needed flashlights, even while setting tents up in the rain about halfway to Homer. We must have pulled into the campground around 1am and slept until 9am.» Full Story »
Sea Kayak Tour
Cypress Island, Puget Sound, Washington, United States
Posted by Cameron on 14 June 2006
The Dickman family from Pennsylvania came to the Great Northwest looking for a unique adventure that would suit their wide age range of children. With two sets of twins, David and Laura at nine years old, Natalie holding the middle ground at twelve, and the two older twins Amy and Maria, sixteen years of age a piece, they needed something equally stimulating and unburdening for the older to support the younger.» Full Story »


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Marjorie Otto/Review • A 6,200 square-foot-expansion, along with roofing and plumbing work, began in 2016 at Johnson High School. The expansion, seen on the east side of the school building facing Arcade Street, includes a new entrance, new administrative offices and five new classrooms.
Two years and $15.9 million later, the construction at Johnson High School is just about finished.
The Denissons spent about 100 hours constructing the bench and donated about $4,000 worth of materials. The bench can seat some 20 people and a commemorative plaque will be added next spring. • submitted photo
As a way to mark their 50-year class reunion, members of the Johnson High School class of 1966 wanted to create or donate something to the school.
They decided on a bench, and not just an ordinary wooden bench, but a big stone "J."
The new entrance and addition will be made of glass and metal to reflect Johnson High School's aerospace program. (courtesy of St. Paul Public Schools)
The changes will take place during the summers of 2016 and 2017
Clogged toilets, wandering visitors and a gloomy entrance that's not handicap accessible are just some of the building-related issues that have plagued Johnson High School.
However, long-awaited building improvements are finally on the horizon. At a District Five Committee for Planning and Economic Development meeting on April 5, community leaders learned of some changes coming to Johnson High School.
Johnson seniors, left to right, Yeng Yang and Va Yang are adapting a Hmong dish to be a possible school lunch offering. (Marjorie Otto/Review)
Seniors Yeng Yang and Va Yang are working to change what they and their classmates eat for lunch at Johnson High School.
The two students are participating in the nationwide culinary contest called Cooking up Change.
Not a yellow bus in sight, students began rolling into Johnson High School around 8 a.m. on a recent Tuesday.
The sun was out, and teens were walking, talking, and yawning as they approach the sprawling school building.
Two students from Johnson High School work on a design to send to a laser engraver. The kids are getting stipends to help staff the Arlington Hills Community Center's Createch Studio, and teach others how to use Johnson High's laser engraver and 3D printer. The equipment is on loan from the school for the summer. (Patrick Larkin/Review)
During the school year, some Johnson High School kids couldn't get enough of the new 3D printers and laser engravers, which came as part of the school's addition of aerospace and engineering curriculum back in 2013.
Starting next fall, Johnson High School will test a later start time. St. Paul Public Schools is considering doing later start times at high schools and middle schools across the district. (Patrick Larkin/Review)
District decides to test later start time on East Side school
For Johnson High School students, it's time to say goodbye to the yellow bus, and hello to Metro Transit.
Starting next September, most Johnson students will be taking public transit to school. And, they'll start school an hour later in the day.
Picture of '47 Johnson High State Hockey Champs (submitted photo)
The date of the 100-year anniversary celebration of the Johnson High School boys hockey team is getting close at hand.
The celebration will be Saturday, Dec. 21, and things are beginning to really heat up for a get-together of East Siders that might prove hard to handle -- especially when it involves old hockey players, with old memories.
The event is billed as "The Pride of the East Side."
submitted photo
Johnson High School principal Micheal Thompson swam with sharks as part of a fundraising effort on Thursday, Nov. 14, Give to the Max Day.
Thompson, along with other principals and faculty, swam in the Sea Life Minnesota aquarium at the Mall of America as Johnson High students watched.
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Tom Cruise is my Rainier
Tom Cruise is really, really good at going super stealth undercover. Not unlike Johnny Depp. And the Brange. When he doesn't want to be found, he will not be found. I wonder why his wife takes a different approach. There are several possible answers, of course, but I haven't decided which one I like best.
Anyway, it's been a while since Tom has allowed photos. Which is probably why several of last week's tabloids starting blaring headlines about their imminent split again. So why not a few pictures to throw them off on Easter weekend? Here they are, Tom, Katie, Little Sci, Connor Cruise, and several members of their families (I've not included those shots but her parents were there too) out in Baton Rouge, Louisiana where Tom has been shooting a new movie. He looks really, really good, right? Like younger than ever.
Click here if you missed Sarah's article earlier in the day about Nicole Kidman playing Grace Kelly saving Monaco in 1962. Prince Rainier was 39 at the time. And looked about 49 (click here to see a photo) which happens to be how old Tom Cruise is right now.
Just... work with me here. Imagine it. Imagine how this would make our lives better.
I mean it would NEVER happen. But I really really wish it could. I really really wish Tom Cruise could play Prince Rainier to Nicole Kidman's Grace. In this case though, even the Gossip Genie couldn't make this real.
By the way, have you ever seen a Tom Cruise/Nicole Kidman wedding photo? I just realised... I don't think I ever have. If you can believe it, I don't think they released it.


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Designed to be stylish as well as protective, our cases will surely make you stand out from the crowd. Made from special polycarbonate material, all our covers are manufactured here in the UK.
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All our products are made to order so make sure you select the right phone model for your case. No returns will be entertained for wrong orders. See FAQ's for more info.
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Applications are now closed. Please sign up for our updated newsletter on our home page, or follow us on Twitter for the latest SproutBox news. In The mean time read through all the information on the site, including the FAQs below. We want to make sure you know as much as possible about SproutBox before you apply.
We're big fans of simple, focused, web based applications that operate on subscription revenue models. That's not to say we aren't interested in other ideas It's just that these types of businesses tend to line up well with our investment criteria.
We look for applicants that have the following characteristics:
Our level of investment and resulting equity stake tends to be higher than a lot of other seed stage funds. Our investments can costs us about $200-250K. During an intense time speriod, we finance your company from as early as idea stage all the way to revenue stage.
If we thought your team/idea mix was worth $1 million, we'd be looking to take an equity stake in the neighborhood of 25%. Our usual equity range is 20-40%. We also typically sign an agreement for a 2-5 year term that allows your company access to ongoing HR, accounting and administrative support in exchange for 5-10% of the company's top line revenue.
We want your company to remain your company. We just want to help you get to a point where you can either operate on your own, or have a great deal of leverage with investors in your next round.
We employ a full-time team of around 10 software developers, creatives and business experts. Along with our network of partners, and your direction, we provide the services needed to take your company from an idea to a revenue-generating reality. In many cases, we utilize pre-built tools (like our billing tool CheddarGetter, or our stock legal documents) to speed up the process. Here is just a short list of the services we offer:
Not much. Essentially, we give founders just enough cash so they can live and stay focused on creating and marketing their product. We also help with a budget for initial marketing and travel. All in, this cash component is usually $10K-20K.
Yes, at least for a while. Around six months in Bloomington is typical. Being here for at least our 3 month long intensive development phase is an absolute must. We have a very collaborative workspace and style. If you're as dedicated to the success of your company as we are, you'll want to be here.
No. We value building companies wherever your family and friends are. Obviously, we love the Bloomington tech scene. Most of us came here for school and loved it so much that we never left. But, once the first version of your product is up and running, the company is yours and you should make decisions about your next steps. We may offer some equity driven incentives to encourage sticking around Bloomington, but the decision will ultimately be yours.
Absolutely. Bloomington has some incredible advantages for startups: Low rent and living expenses, great developers exiting the University, creative and cultural diversity, and a thriving tech scene. As a cultural mecca in the Midwest, it's the perfect place to find focus, fun and tranquility as you build something great. While other companies dropped like flies during the dot-com bust, the SproutBox founders built their previous company here and would tell you that Bloomington was a critical component of their success.
90%+ of incubators are non-profit landlords leasing subsidized office space. Incubation leasing agents are pretty good at their job: keeping their space full. Graduation rates are low and the average incubation period is 2-3+ years. We think this sounds more like assisted living than incubation.
We approach the opportunity in a radically different way. We are for-profit and quickly align our interests in startups by taking equity. We have no incentive to keep you around, in fact exactly the opposite: we kick you out of our space after 6 months. But during that time we've provided all the services and support needed to ensure your success not just fax and copy machines.
Our focus isn't centered exclusively around mentoring and advice. SproutBox is more about tangible product development and business services. We provide a dedicated mentor for each company, as well as one on one lunches with successful business minds, but that is just a portion of the value we provide.
Many seed stage companies employ the 'spray and pray' method investing in 20-60 different companies and hoping a handful are successful. While our projections include a failure rate, our operations don't. We are more selective and more invested in each company's success.
We tend to have a much stronger focus on revenue than other seed stage firms. Many such firms advise entrepreneurs startups not to worry too much about making money. In their model companies are often expected to find additional funding or fail. SproutBox focuses on getting companies 'Revenue Ready'. A clear revenue model is both a selection criteria and goal. If a Sprout seeks additional funding for marketing or product enhancement, it will be to grow, not simply to survive.
SproutBox is the first company of its type in the Midwest. While we welcome entrepreneurs from all over the country, the Midwest is in desperate need of ways to cultivate emerging talent. We also think that the Midwest is a great place to start a web-based company. Its pragmatic sensibilities can shelter companies from the many pitfalls of a struggling economy.
SproutBox is an idea-stage investment company. That being said, the more clearly planned out and developed the idea, the more likely it is to get chosen. Our application includes many questions regarding revenue model, financial projections, entrepreneur background and market research. So a business plan document isn't required, but a plan for your business is. The application also allows you to optionally upload initial screenshots/mockups of your idea to help us gain a better understanding of it. A link to a live site or marketing site never hurts either, but isn't required.
SproutBox is in the unique position of being able to provide a great deal of value to a non-technical entrepreneur. If you have a remarkable marketing mind and great connections, but just need help getting something built, we may be a good fit for you. However, our ideal applicants would be a 2 person team: 1 'business' person and 1 'technical' person who realizes it would take forever to build their idea by themselves. A technical founder is also ideal to help direct our development team and be in good position to continue development after launch.
Maybe. The services we provide are definitely geared toward software products. If you have a great idea for a medical device, there are probably better options for you. We are interested in areas where we can create value. This could include devices with an online component, mobile and desktop software, and likely other ideas we haven't thought of yet.
Absolutely. Established companies often struggle with rounding out their team with quality developers and business experts just like startups. A number of companies have approached us with a secondary product they have developed internally, but can't shift focus entirely to launch it. It may be a well developed system that just needs customer self service and signup along with an initial marketing push. Apply and we'll take a look at it.
We don't share applications outside SproutBox and our selection committee. Because we see stacks of often similar ideas, there is no way we could handle the legal overhead of signing NDAs. Obviously, the more clear you are about your idea, the more likely it is to be chosen. But if you don't feel comfortable including something in your application, don't. More than likely, what you think of as secret isn't going to be the secret to your success. It will be your teams tireless focus on execution. That's why we've always believed ideas are less important than the entrepreneurs that have them.
We believe in constraints. If you have to get to market in a fixed amount of time, you'll have to cut something usually features. Being forced to focus on high margin, core product functionality is a good thing at this stage. We realize that in our time frame we may not be able to fully develop every idea. We will however build a useful product in your market that can serve as a platform for growth.
Not every great idea fits the SproutBox model. That's one of the reasons we are intentionally very selective. In the future, we may expand, but that would mean putting together another world-class team, not just giving individual companies less attention.
We do. We've assembled a group of follow-on investors interested in companies that come out of SproutBox. As much as we like these angels and VCs, our goal is to give you as much leverage as possible in a potential next round. We turn the paradigm upside down. Instead of ramping up expenses and de-emphasizing revenue with your initial funding, companies leaving SproutBox have very little recurring expense and a clear revenue stream. The goal is to get you to the point where fundraising isn't required to keep the doors open. You can raise additional capital to speed growth, or grow just organically. We put your fate in your hands.
No, we accept (and encourage!) applications from all over the world.
Our team reviews applications and will contact the teams that are invited to come pitch in front of our selection team.
It may take a few weeks, but sometimes longer. Sometimes we are able to reach out more quickly. Due to the volume of applications we receive, we aren't always able to respond to each one personally.
If you've got any additional questions please e-mail email@example.com.


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Uber Central lets you order unlimited rides for your guests and customers with no additional fees.
Provide white-glove experiences by offering reliable, on-demand transportation to your customers—no smartphone required.
Arrange and schedule rides for now or later, track them in real time, and let Uber handle transportation for your customers.
Reduce overhead and find peace of mind with upfront pricing and anti-fraud measures. What you see is what you pay.
David Wani, CEO, Twenty Four Seven Hotels
Enter your guest's information along with their desired pickup time and location into Uber Central. We'll take it from there.
Your guest will receive texts with their driver's name and arrival time. No app or smartphone required.
Follow along from the web when your guest is on the way, and get an estimated time of arrival.
Arrange rides for your guests when they need them—now, later, or whenever they're ready—using a feature-rich dashboard that's intuitive and easy to use.
Schedule return and repeat trips in one click—saving time for yourself and streamlining communication with your riders.
Help connect guests with their rides by using smart pickups, which pinpoint the exact pickup or dropoff location. Need to contact the driver? Keep in touch with instant 2-way communication.


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Classic styling with exceptional handling, stability and performance
The ideal cruising boat for many years has been the classic 40 foot sloop. For the first time, thanks to new building technology and design, the comfort and performance benefits of that cruising ideal are now available in 32 feet.
Apart from being more affordable to own and operate, there's an added dimension of comfort in a smaller boat: Maneuverability - landing at a dock or threading through crowded harbors. Furthermore, the J/32 is designed to sail well under mainsail alone and cruise with a small jib rather than genoa. There are no big sails to winch and wrestle and the constant sail changing of heavy displacement cruisers is avoided.
J/32 is traditionally styled with a smooth sweep of the sheerline, low freeboard to reduce wind resistance and facilitate boarding, and a positive transom angle w/swim ladder to maximize deck space. The bow sections are flared to deflect waves downward, keeping the decks dry. Her short overhangs allow a long waterline and superior performance.
The interior is spacious, clean in execution, and beautifully appointed and finished. The owner's cabin is forward, full length settees in the main cabin sleep guests or seat 4-6 for dinner served from a large working galley. The aft sea-head with wet hanging locker and full size navigation table are designed close to the cockpit for comfort and convenience offshore.
Each detail and need has been addressed for equipment and storage for coastal and offshore cruising.
High priority is given to storage in the large galley, nav station and 2 large seat lockers. On deck, the cockpit is large, dodger with side curtains standard, steering comfortable from all positions, and the swim ladder superb.
J/Boats' performance heritage is an invaluable bonus when it comes to quality of construction and many years of problem-free ownership. The 8,300 boats built by the J Boats/TPI partnership have been pushed to the limit by sailors across the oceans of the world. What's more, these same boats come back year after year without losing their performance edge. J/32 represents a significant step forward in cruising with unmatched quality construction throughout.
What the J/32 brings to its size range is the sailing comfort, styling and performance more typically found in cruising yachts of considerably greater length and cost. Advanced composite construction, an easily driven hull shape and a very low center of gravity result in noticeable differences in how J/32 performs compared to any other cruising boat you may have sailed.
Introduced: 1996 Built to: Hull #85 Last Model Year: 2003


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Brewers confident in financial flexibility
MILWAUKEE -- The Brewers took the field Monday with the highest Opening Day payroll in franchise history, but they still have room to make in-season acquisitions, principal owner Mark Attanasio said.
The Brewers' internal payroll figure is higher than the $102,724,338 reported this week by USA Today, because the club budgets for bonuses, midseason callups and other costs. But used as a tool for comparison, the Brewers rank 15th of the 30 teams in spending on players and third in the National League Central, behind the Reds and Cardinals but ahead of the Pirates and Cubs.
"One of the benefits of being conservative fiscally all these years is we will always have flexibility to make moves," Attanasio said. "Maybe not the flexibility of the large-market deals, but if we're in contention at midseason and we need to add people, we will add people, for sure. [General manager] Doug [Melvin] often says the players dictate what we do."
Melvin made that point to the players when he addressed the team in Spring Training.
"I tell the players their performance will take our pulse as to whether or not we go out and get someone to continue a drive to postseason," Melvin said. "We leave it up to them. Their talents and performance will dictate that. I've been in a position before where you're a week before the Trade Deadline and you still don't know. You're always prepared, and Mark's always been there if we needed somebody -- we haven't been afraid to make trades."
By USA Today's standardized measure, third baseman Aramis Ramirez owns the team's highest salary at $15.1 million, followed by right-hander Matt Garza at $12.2 million and second baseman Rickie Weeks at $12 million.


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Ear devices have been on the market for many years and are available in many price ranges. These electronic aids either delay or alter the sound of one's voice, creating an echo, or play some sort of noise, both of which are known to reduce stuttering. However, it is also known that the effects may wear off over time. There is not enough data on the long-term effectiveness of the devices at this time - something the Stuttering Foundation is working to address.
Below is a list of electronic aids, software, and apps. Some people who stutter have found them to be helpful, particularly in limited situations, such as using the telephone or giving a speech.
Three million people in the United States stutter. So far no single method has proven to work for everyone, despite reports of "cures" through new treatments, drugs or devices. For these reasons, the Stuttering Foundation does not endorse any single approach to stuttering treatment.
Instead, we actively support research into the causes of stuttering in the hope of finding ever-better treatments. We encourage you to learn as much as possible about the many treatment options currently available and to choose what is best for your individual situation.
We also offer other resources, including a listings of speech-language pathologists specializing in stuttering therapy. Many of our publications are available free online or at your local library.
You may call us toll-free at 800-992-9392 or e-mail us at email@example.com.
An article on assistive technology
Note: The Stuttering Foundation of America does not warrant the efficacy of these devices nor guarantee their treatment in any way. This page is here for your information only. Appearing on this page is NOT an endorsement by the Stuttering Foundation.
Electronic Devices
Speech Monitor
Rick Arenas
Free Delayed and Frequency Altered Feedback Software: Some people who stutter find that using DAF/FAF helps them to speak more fluently. There are several options to get DAF/FAF by means of software or portable hardware. However, the both the software and hardware options come at a price. Some of the software is relatively cheap, around $25. However, the portable hardware devices are not cheap. They can range anywhere from $1000 to $5000, depending on the size and technology. Speechmonitor.org offers a free resource.
SpeechEasy - $2,500 - $4,500
Janus Development Group, Inc.
112 Staton Road
Greenville, NC 27834
Toll-free (877) 4-Fluency
These devices, worn like traditional hearing aids, use altered auditory feedback in the form of auditory delays & frequency shifts.
Casa Futura Technologies - $295 - $2,495
720 31st Street
Boulder, CO 80303
DAF, FAF, MAF, and stuttering bio feed back devices for clinical, home practice, telephone, and pocket use. 15 States (CA, MA, TX, WI and more) provide funding for anti-stuttering telephone devices to qualified consumers. Schools may inquire about special rates.
KayPentax - $4,000
2 Bridgewater Lane
Lincoln Park, NJ 07035
800-289-5297 (toll-free USA & Canada)
Apps for iPad, iPod Touch, Android, iPhone and other smart phones
The Stammurai, a game created by teens who stutter
Software for Computers
Speech Monitor (free)


text:
Show table of contents
All Cheats & Hints
Rapala: Tournament Fishing Cheats :
This page contains Rapala: Tournament Fishing cheats list for WII version. Now we have 1 cheats in our list, which includes 1 secret. We hope information that you'll find at this page help you in playing Rapala: Tournament Fishing on WII platform. If you didn't find needed cheats put request or ask question about this at special section of the game. Also you can subscribe on all new cheats that we'll find for you in the future!
Secret - Big fish
by Unregistered Aug 31, 2010
In the weight challenge you can reset the boat 4 times and go to the middle of the lake and cast out north west as far as you can. Now go to the bathroom and do your stuff. Good luck!!!!!!!!!!!?
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...to G. A. Michael Sims (Books), aka A Book for all Reasons and ABfaR. We sell second-hand, out-of-print and collectable books. Our stock falls into four main categories:
Naval and military history especially the Royal Naval Patrol Service of WW2
Specific authors from the golden age of modern fiction (1900-1960) notably Dornford Yates
Miscellaneous non-fiction from Architecture to Travel with a good section on East Anglian (Suffolk and Norfolk) local history and topography
Fiction in a variety of genres from crime to sci-fi
You can search our stock or browse the categories. The latter will give you more of a 'real' bookshop experience but the former will give a quick result if you know exactly what you are looking for.
Don't worry about search results or viewing catalogues listing books under an AntiQbook banner. We use AntiQbook to provide the search and database facility for you.


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| 13.4°C Belfast
Stoke boss Mark Hughes has confirmed the club's interest in signing Wolfsburg and Croatia striker Ivica Olic.
Olic, whose contract runs out in the summer, was quoted in the last few days by Croatian newspaper Jutarnji List as saying he had held talks with Hughes and the Potters hierarchy. He said he had been made an offer by the Staffordshire outfit and that he was yet to choose between that and an offer of a new deal from Wolfsburg.
Asked on Friday about the 34-year-old, Hughes said: "It is fair to say he is an interesting player - one I have faced in the past and have always been impressed with.
"There is an interest there and we'll see how it progresses."
Hughes has also given his thoughts on the contract situations of Stoke stalwart Andy Wilkinson.
Defender Wilkinson, a Potters academy graduate, is on a deal that expires at the end of the season.
He has already indicated he has been offered a new one and that, despite his frustration at a lack of game time this term, he hopes to stay put.
Hughes said of the 29-year-old: "We'd like Andy to stay - I think he typifies the Stoke attitude and he has good ability.
"He is a local guy, has been here a long time and is very much part of the fabric of the place, and you can't have too many of those type of players in your club.
"So we'll be delighted if Andy can agree a new deal and is here for a longer time."
Stoke will check on the condition of Peter Odemwingie ahead of Saturday's Barclays Premier League home clash with Arsenal after he sustained a calf problem.
Fellow Potters forward Jon Walters has missed a couple of days of training this week due to illness but is expected to be available, and on-loan Manchester City striker John Guidetti is eligible once again after sitting out last weekend's defeat at his parent club.
Defender Robert Huth, who last played for the Stoke first team in November and has been recovering from knee surgery, successfully came through 45 minutes of a behind-closed-doors friendly on Tuesday but is not yet ready for a competitive return. On-loan Liverpool winger Oussama Assaidi (knee) remains sidelined.
Mesut Ozil will return after hip trouble and a two-day rest for Arsenal.
Gunners boss Arsene Wenger will leave a decision on whether or not to field fit-again defender Thomas Vermaelen at left-back to the last minute.
Nacho Monreal (ankle) and Kieran Gibbs (gluteus) both remain doubtful, and if neither make it back in time for the Potters clash, Wenger could deploy Vermaelen, fully recovered from a shin problem, on the left of his defence
Tony Pulis' muscular Stoke side intimidated Arsenal's cosmopolitan crew into untold headaches over the years, but now new boss Hughes is battling to expand that regimented game plan.
Wenger admitted Arsenal may be more suited to taking on a team built by the former Manchester United and Wales striker than facing up to Pulis' pressgang tactics.
"We had some bad memories but also some good ones as well," said Wenger.
"It's a stadium where before, first of all the pitch was narrow and difficult to play, a bit more open to the wind.
"But recently we have shown as well it's down to the performance on the day.
"If you perform on Saturday that's all that counts.
"Yes it probably is better for us now though, because we went sometimes to Stoke, who had a rough style, we had young players and it was difficult.
"But they have good players, they have done well in the league, they qualified for the Europa league.
"So they are a real challenge.
"Every manager has his own style, he (Hughes) has experience and has shown he can do well.
"Given time he will print his own style of play."


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|Working Group I: The Scientific Basis
|Other reports in this collection
Executive Summary
The results presented in this chapter are based on simulations made with global climate models and apply to spacial scales of hundreds of kilometres and larger. Chapter 10 presents results for regional models which operate on smaller spatial scales. Climate change simulations are assessed for the period 1990 to 2100 and are based on a range of scenarios for projected changes in greenhouse gas concentrations and sulphate aerosol loadings (direct effect). A few Atmosphere-Ocean General Circulation Model (AOGCM) simulations include the effects of ozone and/or indirect effects of aerosols (see Table 9.1 for details). Most integrations1 do not include the less dominant or less well understood forcings such as land-use changes, mineral dust, black carbon, etc. (see Chapter 6). No AOGCM simulations include estimates of future changes in solar forcing or in volcanic aerosol concentrations.
There are many more AOGCM projections of future climate available than was the case for the IPCC Second Assessment Report (IPCC, 1996) (hereafter SAR). We concentrate on the IS92a and draft SRES A2 and B2 scenarios. Some indication of uncertainty in the projections can be obtained by comparing the responses among models. The range and ensemble standard deviation are used as a measure of uncertainty in modelled response. The simulations are a combination of a forced climate change component together with internally generated natural variability. A number of modelling groups have produced ensembles of simulations where the projected forcing is the same but where variations in initial conditions result in different evolutions of the natural variability. Averaging these integrations preserves the forced climate change signal while averaging out the natural variability noise, and so gives a better estimate of the models' projected climate change.
For the AOGCM experiments, the mean change and the range in global average
surface air temperature (SAT) for the 1961 to 1990 average to the mid-21st century
(2021 to 2050) for IS92a is +1.3°C with a range from +0.8 to +1.7°C
for greenhouse gas plus sulphates (GS) as opposed to +1.6°C with a range
from +1.0 to +2.1°C for greenhouse gas only (G). For SRES A2 the mean is
+1.1°C with a range from +0.5 to +1.4°C, and for B2, the mean is +1.2°C
with a range from +0.5 to +1.7°C.
AOGCMs can only be integrated for a limited number of scenarios due to computational expense. Therefore, a simple climate model is used here for the projections of climate change for the next century. The simple model is tuned to simulate the response found in several of the AOGCMs used here. The forcings for the simple model are based on the radiative forcing estimates from Chapter 6, and are slightly different to the forcings used by the AOGCMs. The indirect aerosol forcing is scaled assuming a value of -0.8 Wm-2 for 1990. Using the IS92 scenarios, the SAR gives a range for the global mean temperature change for 2100, relative to 1990, of +1 to +3.5°C. The estimated range for the six final illustrative SRES scenarios using updated methods is +1.4 to +5.6°C. The range for the full set of SRES scenarios is +1.4 to +5.8°C.
These estimates are larger than in the SAR, partly as a result of increases in the radiative forcing, especially the reduced estimated effects of sulphate aerosols in the second half of the 21st century. By construction, the new range of temperature responses given above includes the climate model response uncertainty and the uncertainty of the various future scenarios, but not the uncertainty associated with the radiative forcings, particularly aerosol. Note the AOGCM ranges above are 30-year averages for a period ending at the year 2100 compared to the average for the period 1961 to 1990, while the results for the simple model are for temperature changes at the year 2100 compared with the year 1990.
A traditional measure of climate response is equilibrium climate sensitivity derived from 2xCO2 experiments with mixed-layer models, i.e., Atmospheric General Circulation Models (AGCMs) coupled to non-dynamic slab oceans, run to equilibrium. It has been cited historically to provide a calibration for models used in climate change experiments. The mean and standard deviation of this quantity from seventeen mixed-layer models used in the SAR are +3.8 and +0.8°C, respectively. The same quantities from fifteen models in active use are +3.5 and +0.9°C, not significantly different from the values in the SAR. These quantities are model dependent, and the previous estimated range for this quantity, widely cited as +1.5 to +4.5°C, still encompasses the more recent model sensitivity estimates.
A more relevant measure of transient climate change is the transient climate response (TCR). It is defined as the globally averaged surface air temperature change for AOGCMs at the time of CO2 doubling in 1%/yr CO2 increase experiments. The TCR combines elements of model sensitivity and factors that affect response (e.g., ocean heat uptake). It provides a useful measure for understanding climate system response and allows direct comparison of global coupled models. The range of TCR for current AOGCMs is +1.1 to +3.1°C with an average of 1.8°C. The 1%/yr CO2 increase represents the changes in radiative forcing due to all greenhouse gases, hence this is a higher rate than is projected for CO2 alone. This increase of radiative forcing lies on the high side of the SRES scenarios (note also that CO2 doubles around mid-21st century in most of the scenarios). However these experiments are valuable for promoting the understanding of differences in the model responses.
Continues on next page
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text:
Christina Megerle
Harrah's New Orleans Casino
New Orleans, Louisiana
"Christina Megerle"
Excellent service and wonderful food!!! We went there to there for our 6th anniversary and was impressed! My husband said he had the best ribeye he ever had. We live in Columbus ohio but if I'm ever in town I would definitely be back. It's a must????????


text:
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text:
You would think the pain would be too much for Gwen Ward, but she still keeps going back to the school just two blocks away from the intersection where her 15-year-old daughter, Christina Morris-Ward, was stuck by a car and killed.
It happened 10 months ago on Halloween morning. Outgoing and opinionated, Christina was a typical teenager in all the right ways. Most of the time she got a ride to school with her mom, but Gwen got off to an early start that morning, so Christina walked to Seneca Valley High School. Dressed in dark clothes and wearing headphones, Christina was glancing down at her phone as she crossed the street just blocks away from her school. But before she got to the other side of the intersection, an oncoming car hit her.
By the time Gwen arrived at the hospital, it was too late, and Gwen was left trying to make sense of this tragedy and all the things that could have been done to prevent it. The loss still haunts Gwen. But regardless of the pain, she keeps going back to the school. That's where the kids are, so that's where she needs to be to raise awareness and educate other students about the dangers of distracted walking. She says it's therapeutic even if it doesn't completely take away the pain.
She works with the school, government officials, the police department and many of Christina's friends. Together, they talk to teens and kids of all ages about how to walk safely to school. They distribute reflectors for kids to wear when it gets dark and urge them to put down their devices when crossing the street. Gwen continues to tell her story as a way to keep Christina's legacy alive -- doing everything she can to make sure this tragedy doesn't happen to anyone else.
Unfortunately, it's been happening too often lately and we're moving in the wrong direction.
According to a study by my organization, one in five high school students and one in eight middle school students cross the street while distracted and it can lead to deadly results. Teens now account for half of all pedestrian deaths among children 19 and under.
The good news is the solution isn't complicated even if implementing it is. Mobile devices are part of everyday life, which can provide positive benefits in many ways. But we all need to work together to find a way to encourage teens and everyone to put these devices down when they're crossing the street.
We came up with one idea. It's called the Moment of Silence campaign. It's easy to participate: In memory of Christina and the thousands of other teens who have been injured or killed while crossing the street, simply commit to putting your device down and paying attention when crossing the street.
Watch this video to learn more.
Safe Kids Worldwide and FedEx are launching a national effort calling on parents and teens to put devices down and keep heads up when crossing the street, to reverse the dangerous trend of pedestrian injuries caused by distraction. Learn more about the issue and join the Moment of Silence campaign at safekids.org.


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- WiFi
- Car park
- Air conditioning
- Spa
- Airport Shuttle
- Accessible
- Sports
- Gym
- Business
Choose your room
In the name of our entire staff, we welcome you happily to the Hotel Selcuk.
If you are travelling by car or bike, we have secure parking for bikes and ample car parking spaces available.
Hotel guests can take advantage of our convenient car parking space. Please request when making a booking.
Free for you
The use of the hotel sauna is included in your stay and comes at no extra cost.
During your stay, you can park for free at the hotel.
We have a safe and reliable shuttle service from the airport to our hotel.
We provide guests with a shuttle service to the airport.
Make yourself at home
We offer you a strong box for the storage of your articles of value while you are staying in the hotel.
Our welcoming features a lift for guests of our hotel.
The lobby has video surveillance.
Culinary greetings from the kitchen
The hotel's acclaimed restaurant as well as our atmospheric bistro-café cater for all your culinary needs.
The hotel's restaurant also provides halal meals.
Where you will stay
Your room's desk is perfect in case you brought your work back to the hotel.
A minibar stocked with a large amount of beverages, an easy-to-use telephone as well as cable television can be found in your room.
For your convenience, we have a shower, a bathtub and a hairdryer located in our bathrooms.
For your enjoyment, our hotel has soundproof windows.
Relax or be active
We offer our guests a sauna.
You will enjoy your work-out in the fully equipped fitness room.
Business hours of reception:
On business days: from 00:00 to 00:00 and from 00:00 to 00:00
On the weekend: from 00:00 to 00:00 and from 00:00 to 00:00
Useful information:Other names for Selcuk Hotel:
Selcuk Mevlana