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Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
Tollenaar, R. A. E. M.
van den Ouweland, Ans M. W.
BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.
Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965-1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or >or=2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.
Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.
The MRE11, RAD50, and NBS1 genes encode proteins of the MRE11-RAD50-NBS1 (MRN) complex critical for proper maintenance of genomic integrity and tumour suppression; however, the extent and impact of their cancer-predisposing defects, and potential clinical value remain to be determined. Here, we report that among a large series of approximately 1000 breast carcinomas, around 3%, 7% and 10% tumours showed aberrantly reduced protein expression for RAD50, MRE11 and NBS1, respectively. Such defects were more frequent among the ER/PR/ERBB2 triple-negative and higher-grade tumours, among familial (especially BRCA1/BRCA2-associated) rather than sporadic cases, and the NBS1 defects correlated with shorter patients' survival. The BRCA1-associated and ER/PR/ERBB2 triple-negative tumours also showed high incidence of constitutively active DNA damage signalling (gamma H2AX) and p53 aberrations. Sequencing the RAD50, MRE11 and NBS1 genes of 8 patients from non-BRCA1/2 breast cancer families whose tumours showed concomitant reduction/loss of all three MRN-complex proteins revealed two germline mutations in MRE11: a missense mutation R202G and a truncating mutation R633STOP (R633X). Gene transfer and protein analysis of cell culture models with mutant MRE11 implicated various destabilization patterns among the MRN complex proteins including NBS1, the abundance of which was restored by re-expression of wild-type MRE11. We propose that germline mutations qualify MRE11 as a novel candidate breast cancer susceptibility gene in a subset of non-BRCA1/2 families. Our data have implications for the concept of the DNA damage response as an intrinsic anti-cancer barrier, various components of which become inactivated during cancer progression and also represent the bulk of breast cancer susceptibility genes discovered to date.
BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.
Objectives To examine possible associations between socioeconomic status, management and survival of patients with non-small cell lung cancer (NSCLC). Methods In a population-based cohort study, information was retrieved from the Regional Lung Cancer Register in central Sweden, the Cause of Death Register and a social database. ORs and HRs were compared to assess associations between educational level and management and survival. Results 3370 eligible patients with an NSCLC diagnosis between 1996 and 2004 were identified. There were no differences in stage at diagnosis between educational groups. A higher diagnostic intensity was observed in patients with high compared with low education. There were also social gradients in time between referral and diagnosis in early stage disease ( median time: low, 32 days; high, 17 days). Social differences in treatment remained following adjustment for prognostic factors ( surgery in early stage disease, high vs low OR 2.84; CI 1.40 to 5.79). Following adjustment for prognostic factors and treatment, the risk of death in early stage disease was lower in women with a high education ( high vs low HR 0.33; CI 0.14 to 0.77). Conclusion The results of this study indicate that socioeconomically disadvantaged groups with NSCLC receive less intensive care. Low education remained an independent predictor of poor survival only in women with early stage disease. The exact underlying mechanisms of these social inequalities are unknown, but differences in access to care, co-morbidity and lifestyle factors may all contribute.
Lymphomas are a heterogeneous group of neoplasias originating from B- or T-lymphocytes. In this thesis, we determined the genetic and immunophenotypic characterization of DLBCL and their prognostic impact. Moreover, genomic alterations associated with the transformation to DLBCL from Hodgkin lymphoma (HL) and follicular lymphoma (FL) were elucidated.
In order to outline the impact of cytogenetic as well as immunophenotypic prognostic markers in DLBCL, we firstly studied a series of 54 DLBCL tumors using comparative genomic hybridization (CGH) and we identified several frequently occurring chromosomal imbalances. Loss of 22q was more often found in the diagnostic tumors with a more advanced clinical stage, while gain of 18q21 was more commonly identified in relapses. Secondly, we correlated the expression patterns of CD10, bcl-6, IRF-4 and bcl-2 with clinical parameters in a series of 173 de novo DLBCL patients. Patients with a germinal center (GC) phenotype displayed a better survival than the non-GC group. Expression of bcl-6 and CD10 was correlated with a better survival while bcl-2 expression was associated with a poor prognosis.
In approaching the HL transformation, two novel B-cell lines (U-2932 and U-2940), derived from patients with DLBCL following HL, were characterized. Interestingly, a translocation with materials from 2q and 7q as well as loss of material on 6q was found in both cell lines. For FL transformation, we assessed chromosomal alterations in a panel of 28 DLBCL patients with a previous history of FL. The DLBCL tumors displayed more chromosomal imbalances compared to FL tumors. Loss of 6q16-21 and gain of 7pter-q22 were more commonly found in the DLBCL counterparts, suggesting the chromosomal location of putative genes that may be involved in the transformation process.
In Sweden approximately 2800 new lung cancer patients are diagnosed every year. Radiotherapy is used with curative intention in certain groups of patients. The aim of this thesis is to study the basis of differences in radioresistance and the possibility to predict response to radiotherapy.
In the first study we investigated, using the comet assay, four lung cancer cell lines with different sensitivity towards radiation. A clear dose-response relationship for radiation-induced DNA single strand and double strand breaks were found. All cell lines showed a remarkably efficient repair of both the DNA single strand and double strand breaks one hour after irradiation. However, further studies in one radioresistant and one radiosensitive cell line demonstrated that repair during the first 15 min had the best accordance with radiosensitivity measured as surviving fraction.
In the second and third study, sequencing studies of the p53 gene were performed on cell lines as well as on tumour material. Cell lines that were expressing a mutation in exon 7 were associated with increased radiosensitivity compared with tumor cell lines with mutations in other exons. In the clinical study, 10 patients were found to be mutated in the p53 gene whereas the other 10 patients were not. No correlation to clinical parameters could be drawn.
In the fourth study, serum from 67 patients with a confirmed diagnosis of non-small cell lung cancer was investigated for the presence of p53 antibodies. P53 antibodies in sera, taken prior to radiation treatment, were associated with increased survival.
The summary of this thesis indicates that the p53 gene has an impact on the effect of radiotherapy in lung cancer. The presence of p53 antibodies might be of clinical interest for predicting survival after radiotherapy. Further studies on the importance of the p53 gene on early repair are of interest.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
For a PET agent to be successful as a biomarker in early clinical trials of new anticancer agents, some conditions need to be fulfilled: the selected tracer should show a response that is related to the antitumoral effects, the quantitative value of this response should be interpretable to the antitumoral action, and the timing of the PET scan should be optimized to action of the drug. These conditions are not necessarily known at the start of a drug-development program and need to be explored. We proposed a translational imaging activity in which experiments in spheroids and later in xenografts are coupled to modeling of growth inhibition and to the related changes in the kinetics of PET tracers and other biomarkers. In addition, we demonstrated how this information can be used for planning clinical trials. Methods: The first part of this concept is illustrated in a spheroid model with BT474 breast cancer cells treated with the heat shock protein 90 (Hsp90) inhibitor NVP-AUY922. The growth-inhibitory effect after a pulse treatment with the drug was measured with digital image analysis to determine effects on volume with high accuracy. The growth-inhibitory effect was described mathematically by a combined E-max and time course model fitted to the data. The model was then used to simulate a once-per-week treatment, in these experiments the uptake of the PET tracers F-18-FDG and 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT) was determined at different doses and different time points. Results: A drug exposure of 2 h followed by washout of the drug from the culture medium generated growth inhibition that was maximal at the earliest time point of 1 d and decreased exponentially with time during 10-12 d. The uptake of F-18-FDG per viable tumor volume was minimally affected by the treatment, whereas the F-18-FLT uptake decreased in correlation with the growth inhibition. Conclusion: The study suggests a prolonged action of the Hsp90 inhibitor that supports a once-per-week schedule. F-18-FLT is a suitable tracer for the monitoring of effect, and the F-18-FLT PET study might be performed within 3 d after dosing.
The aim of this study was to evaluate the usefulness of coincidence PET imaging as compared with dedicated PET/CT in cancer staging. Patients and Methods: Sixteen patients with thoracic malignancies referred to a PET/CT examination accepted to repeat the acquisition with a coincidence PET system. One experienced nuclear medicine physician compiled a report from the PET/CT examinations and the coincidence PET images. The reports were compared and evaluated according to the degree of agreement: no agreement, unsatisfactory, acceptable or satisfying agreement. Results: Satisfying or acceptable agreement between the PET/CT and the coincidence PET examination was found in 14 out of 16 patients (88%). The main issue for the examining physician was to anatomically locate the FDG uptake in the mediastinum in The coincidence PET images. Conclusion: The data from this small study imply that the staging results obtained with coincidence PET are in most cases concordant with those obtained with dedicated PET/CT.
BACKGROUND: To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00-CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models. RESULTS: Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of >= 50% vs <50%. CONCLUSION: In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient's perception needs to be taken into account.
The purpose was to analyze survival of patients with colorectal cancer and a positive family history for colorectal cancer in first degree relatives compared with those with no such family history and to determine whether differences in survival could be explained by known clinico-pathological factors. During 2000-2003, 318 consecutive patients with colorectal cancer answered a written questionnaire about their family history for colorectal cancer. During a 6-year follow-up, recurrences and survival were registered. Thirty-one (10%) patients had a first-degree relative with colorectal cancer, moreover two patients fulfilled the criteria of hereditary non-polyposis colorectal cancer and were excluded. Patients with a first-degree relative with colorectal cancer had better survival and lower risk for recurrences compared to those with no relatives with colorectal cancer. In a multivariate analysis including age, gender, stage of disease, tumor differentiation, vascular invasion and family history, patients with first-degree relatives with colorectal cancer had lower risks for death (RR 0.37; 95% CI 0.17-0.78) and death from cancer (RR 0.25; 95% CI 0.08-0.80), compared to those with a no relative with colorectal cancer. The differences were seen in patients with colon cancer but not rectal cancer. Family history for colorectal cancer in a first-degree relative is an individual prognostic factor in patients with colon cancer and could not be explained by known clinico-pathological factors. The value of family history taking in patients with colon cancer is therefore not only to identify families with hereditary colorectal cancer, but also to add information to the prognosis of the patients.
Background: Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC. Patients and methods: During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms. Results: High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels. Conclusions: This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.
BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.
Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.
This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.
In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.
In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.
We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.
DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.
None of the investigated markers in study III and IV correlated with disease free survival or overall survival.
In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
BACKGROUND: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. PATIENTS AND METHODS: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. RESULTS: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). CONCLUSION: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.
PURPOSE: Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate. PATIENTS AND METHODS: The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109). RESULTS: The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity. CONCLUSION: CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.
This thesis investigated the predictive and the prognostic powers of angiogenesis related markers in both operable and inoperable non-small cell lung cancer (NSCLC) patients.
In the first and second study, we investigated the serological fractions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 2 cohorts of patients with either operable or inoperable NSCLC.
Regarding operable NSCLC, we demonstrated significant correlations between VEGF and tumour volume and overall survival. Regarding bFGF, significant correlations with recurrent disease and survival were demonstrated. VEGF and bFGF correlated to each other and with platelet counts. In multivariate analysis, bFGF proved to be a significantly independent prognostic factor.
Regarding inoperable NSCLC, we demonstrated that patients with elevated bFGF levels before any treatment and during chemotherapy had a significantly poorer survival. During chemotherapy, each rise of one unit of bFGF (ng/L) corresponded to a 4 times increased risk of death. Regarding VEGF, elevated levels after radiotherapy corresponded with better survival. All prognostic information demonstrated in this study concerned patients with a, co-sampled, normal platelet count.
In the third study, three putative markers, HER-2, EGFR and COX-2, suitable for targeted therapies in resected NSCLC were investigated in a panel of 53 tumours and further investigated for a possible correlation with microvessel density. We demonstrated that HER-2 and COX-2 were mainly expressed in adenocarcinomas, whereas EGFR was only expressed in squamous cell carcinomas. COX-2 showed a trend towards a correlation with microvesssel density. The expression profile, HER-2+/EGFR-, was significantly correlated to poorer survival.
In the fourth study, a predictive model for recurrences consisting of p53, CD34 and CD105, and circulating serum fractions of VEGF and bFGF, was investigated. The two endothelial markers correlated with each other. CD105 expression correlated with p53 expression. No other significant correlations between markers could be demonstrated. A significant correlation between p53 overexpression and recurrent disease was demonstrated. The mutational status could not confirm the immunohistochemical correlation between p53 and recurrences.
In conclusion, the present thesis demonstrates that the angiogenic factors VEGF and bFGF analysed in sera have both predictive and prognostic information when measured in operable and inoperable NSCLC. Since HER-2 is overexpressed in NSCLC and linked with prognostic information, this marker might be a suitable target for therapy in NSCLC. Furthermore, in patients with operable NSCLC, p53 expression status was linked with recurrent disease and mean MVD.


text: Let's move on to the mouth. Just keep in mind that less is more. You don't need much to really make this feature come to life.

industry_corpus2: Others


text: Among the modelling approaches that have been proposed for the simulation of wildfire propagation, two have gained considerable attention in recent years: the one based on a reaction-diffusion equation, and the one based on the level set method. These two approaches, traditionally seen in competition, do actually lead to similar equation models when the level set method is modified taking into account random effects as those due to turbulent hot air transport and fire spotting phenomena. The connection between these two approaches is here discussed and the application of the modified level set method to test cases of practical interest is shown.

industry_corpus2: Safety Management


text:
Trey, and 140 other children from OCCC’s Child Development Center and Lab School, recently displayed artwork for the 2013 Art Show which ran from April 15 through 19 at the FACE Center.
The children learn more effectively through hands-on crafts, such as art, said Lee Ann Townsend, lab supervisor. The children, ranging in age from 6 weeks through 8 years, engage in daily group activities and projects.
The art show is a fun way to show people what the children do at their school, Townsend said. The art show is an annual event put on by the children’s center in celebration of the Week of the Young Child, April 14 through 20, Townsend said.
The Art show featured more than 200 pieces. The images included abstract art, bush babies, rocket ships (complete with passengers), engines and emergency exit.
To prove his point, Trey drew a picture on the spot to give the Pioneer reporter as a souvenir of her visit to the center.
The Family and Community Education Center is located at 6500 S. Land Ave. in Oklahoma City.

industry_corpus2: Subject Education


text:
Divorce or dissolution of marriage is the final termination of marriage, canceling the legal duties and responsibilities of marriage.
We strongly recommend that prior to making the final decision to divorce, that you seek help for your marriage from therapists, doctors, clergy or marriage counselor.
Anyone that you both feel comfortable with. This is especially important to think about if there are children involved.
The legal process for divorce may also involve issues of spousal support, child custody, child support, distribution of property and division of debt, retirement accounts. The list goes on and on.
We would like to help facilitate the divorce in a peaceful, balanced and fair manner. There is no benefit to long litigation for most divorces.
There are divorces when one side is being unreasonable, refuses to adhere to court orders, drags out the process and generally drags out the process. If that is you, STOP IT. If your soon-to-be ex is the culprit and your case is getting "out of hand" Call us immediately.
Research and common sense both tell us that children are better off with two parents involved in their lives rather than one. At Singer & Associates Law Office, A Fathers Custody Center, Inc., we fight every day to help loving fathers retain their parental rights and maintain the relationships so crucial to the emotional well-being of their children.
Too often courts exhibit a bias against fathers. For years our Sacramento, California firm has successfully battled that bias, helping judges to understand both sides of a failed marriage. When possible, our approach is to work with the other side to come to reasonable agreements on parenting and other disputes. If it's not possible to work with the other party, we do what's necessary to protect our client's rights and achieve their goals in family court.

industry_corpus2: Law & Justice


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It doesn’t take much to fall in love with Allison and Matt. They light up a room with their contagious joy and kindness. Their wedding was heartfelt and real with loads of laughter, smiles and confetti to boot.
// Matt and Allie’s beautiful Mennonite Heritage Village Wedding can also be found in the December 2015 issue of WEDDING BELLS MAGAZINE and online.
– Allison’s summary of her wedding day snagged from the article in Wedding Bells Magazine.
The wedding took place at The Mennonite Heritage Village in Steinbach. Allison’s gown was designed by Mori Lee and purchased from Say Yes Bridal in Winnipeg. Suits designed and purchased from EPH Apparel, Winnipeg. Catering provided by Urban Praire Cousine and linens were provided by Let’s Celebrate Rentals.


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Specify the name of the Capistrano task to be executed.
Specify the list of the arguments to be passed to the Capistrano task. The arguments should be separated with spaces.
Select the desired stage. Stages can be configured in the config/deploy.rb file that appears after capifying an application.
Select this checkbox to turn on the standard Capistrano --trace option.

industry_corpus2: Computing & Telecommunications


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Network Marketing for Retirement Planning?
If you are like most people approaching that “golden age of retirement”, you are probably more than a little shocked at how little “gold” you have acquired and managed to save. You are definitely not alone. The average 50 year old has less than $50,000 in retirement savings. The idea of being able to retire and sit around doing nothing while slowly depleting that nest egg from age 62 to 100 is something more and more people are coming to terms with.
Most of us understand “retirement planning” as a way to somehow amass enough money in a retirement account or accounts and then live off the interest until our time on earth is through. But there are a lot of baby boomers who are starting to be burdened with a little guilt and shame about past saving and spending habits. The search for solutions is on and more people are beginning to discover that network marketing may very well provide that solution.
While most of us think about “retirement” as that time of life where we can finally stop working, AARP estimates that half of all baby boomers (76 million) are actually interested in starting a business of their own.
Money is definitely a big factor in retirement planning but there is actually more to the story. Many baby boomers are simply tired of their current careers. They are worn out from years of dealing with the corporate grind. They feel more and more disconnected from their job and how it may not be having the sort of impact they truly desire, not only in their own lives but in the lives of those impacted outside the corporate cubicle. For many, the desire is to be part of something more, to have a positive impact on the lives of others, and they actually want something to DO during their retirement years.
So why are so many ready to consider network marketing as a possible alternative? The first thing that appeals to many candidates is the low barrier to entry. Many network marketing businesses can be started for a few hundred dollars. In addition, good network marketing companies provide training, support, encouragement, and motivation along the way.
In addition to money, retirees and future retirees are realizing that they need activities to keep them busy, connected, active, and in good health. The time, energy, and money spent makes network marking a very appealing possibility for large segments of the population.
Not everybody wants to be a big hitter. Some folks simply want to be able to cut their regular office hours back while being more available to their family and have more freedom to enjoy an active social life.
Maybe they will use the money to travel more, spend more time with the grand kids and children, or just take more time to themselves. Maybe having more free time will help them lose weight, find time to learn to cook, etc… Maybe they will be able to turn their passion for cosmetics and skin care in to an additional income stream. Whatever the motivation, network marketing can be a solid resource to make these things happen.
Those that do want to be “big hitters” understand and follow a common theme among other big hitters in the network marketing industry: “If you treat it like a hobby, don’t expect it to pay you like a business”. Those entrepreneurs that reach the 5 and 6 figure monthly income levels are typically working much harder on their network marketing business than they ever worked on their job. But the other side of the coin is that they love what they are doing, feel great about the impact they are having on the lives of others, and enjoy the freedom to choose how far they want to take their business.
It is my sincere belief that network marketing is an important consideration for anyone entering retirement or getting close to retirement.
About The Author: Brian Rooney escaped the rat race in the year 2000 by starting his own home based business. Since that time, Mr. Rooney has provided tools and training for thousands of network marketing professionals via his internet marketing services. If you are looking for a home based business for yourself, be sure to view the listings at TheOnlineAdNetwork.com.
You’re very welcome! I hope you found it to be helpful.
Brian: EXCELLENT Article! It just makes so much sense to work quality network marketing programs in with one’s retirement planning, especially if the Golden Years are falling a bit short cash flow wise.
It’s always amazed me that people 55+ will take low paying jobs at Walmart, 7-11,etc. to make some extra cash when they could make SO MUCH MORE by introducing their fellow Golden Years friends to the power of leverage and network marketing.
The key is to only marketing and introduce quality programs that have embedded value propositions and it’s simple to build from there.
Thanks again Brian, really good stuff!
That has always amazed me when someone has to return to a regular job that has already proven to fall short of what is really needed. I suppose that’s part of our job description: Helping folks learn that there just might be a better way!
Do you know more about retirement? What are you hope to get from this important life stage? How will you save enough money? . Take some time consider and read this advice to get more information.
Contribute regularly and take full advantage of any employer match that is provided. That’s pretty much free money in your pocket, you can save greater amounts through this because the money before tax is taken off it when you invest in a 401k.If the employer matches contributions.
While it is important to put away as much as you can for retirement, thinking about the types of investments to make is also important. Diversify your investment portfolio and make sure that you do not put all your eggs in one place. This will minimize your portfolio very strong.
Consider waiting a few extra years to take advantage of Social Security. This will increase the amount of money you ultimately receive. This is a particularly good idea if you can still work or have another source of income.
Many people put off doing the opportunity to accomplish their dreams. Time certainly seems to slip by faster the more we get older.
Think about getting a long-term health plan for the long term. Health often declines as they age. In some cases, such a deterioration of health escalates health care costs. If you have factored this into your plan, you will be able to have the help you need at home or in an adult living center or nursing home.
Find out about pension plans. Learn all that will help you with. See if your prior employer offers you with benefits. Your spouse’s pension program may offer you benefits too.
There are many things to consider when planning for retirement. Follow the advice presented here to do well in retirement. Use these tips when planning for retirement.

industry_corpus2: Finance & Economics


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Efficient positioning where passengers shop every day.
With around 42,000 m2 of retail space, Frankfurt Airport is one of the region’s biggest shopping malls.
In the vicinity of the Airport City Mall, Shopping Avenue and Waiting Hall B airside, you can present your brands, products and special offers on Wall Panels of up to 10 meters in length.
Unique target-group mix of business and holiday travelers, visitors, meeters & greeters and over 70,000 airport employees.
There are also locations in the vicinity of the Car Rental Center – the ideal place to make contact with business and frequent travelers.

industry_corpus2: Transportation


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Our TDQ (Training, Development & Qualification) regular Q&A and this issue’s article looks at the JO3 and AF2 exams.
Finally, our monthly Parameters survey sought your views on the potential impact of Brexit on financial planning for clients and the work of paraplanners.
We also announce the dates and locations of our Technical Insight Seminars 2019.
As some of our events last year were oversubscribed, now is the time to register your interest in one of the 15 locations we aim to reach next year, bringing the seminars closer to many more paraplanner around the country.


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MANTA Product Development is a clever, award winning, full service product design consultancy working in a broad range of product areas, especially medical, consumer, robotics, pharmaceutical, business/industrial and sporting goods. MANTA has designed products for companies such as Rethink Robotics, Philips, Salomon, Eli Lilly, Hologic, Smith & Nephew and iRobot. MANTA focuses on optimizing user experience and on building relationships with clients that foster innovation.
Manta's services include industrial design, mechanical engineering, design research, usability, and ergonomics.

industry_corpus2: Biopharmaceuticals


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The East Clinton reserve boys basketball team lost a close one Friday to Williamsburg, 42-38.
Quinton Tolle led the Astros with 12 points.
Taylor McComas had 11 points and Landon Runyon scored eight for Roger Earley’s squad.

industry_corpus2: Sports


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The oil industry vigorously opposed efforts to list the threatened dunes sagebrush lizard as an endangered species. But three oil company lobbyists were given day-to-day oversight of the effort to save the reptile.
When Texas promised to protect a threatened lizard in the oil-rich Permian Basin, state officials entrusted the day-to-day oversight to a nonprofit that sounds like an environmental group: the Texas Habitat Conservation Foundation.
What’s not advertised is the occupation of the board members who created it.
They are all registered lobbyists for the powerful Texas Oil and Gas Association, also known as TXOGA.
The industry group's prominent role in the fate of the dunes sagebrush lizard has angered both environmentalists and influential GOP lawmakers who want to reform the way Texas oversees threatened and endangered species. The flap has also exacerbated traditional tensions between corporate oil interests and independent producers, and it has put Comptroller Susan Combs in the crosshairs of some fellow Republicans.
The controversy has its origins in the special session of 2011, when then-state Rep. Warren Chisum, R-Pampa, slipped an amendment onto the innocuous-sounding “fiscal matters” bill that had to pass because it provided badly needed revenue for a cash-strapped Legislature.
Chisum’s amendment, which he said was pushed by the oil and gas association, granted key state authority over the handling of endangered species matters to the office of the comptroller, a role that has traditionally been played by the Texas Parks and Wildlife Department, officials said.
“There was a group of us, the people from TXOGA, and we said we need to get this done," Chisum told The Texas Tribune. "That’s how it got started. Of course, we brought the comptroller in."
The U.S. Fish and Wildlife Service had already proposed listing the lizard as endangered by then, a move strongly opposed by TXOGA and others in the oil industry, along with virtually any Texas Republican near a microphone.
In response, Combs, working with the oil industry, landowners, local government officials and others, proposed a voluntary program to protect the dunes sagebrush lizard. The idea was to forestall a declaration or “listing” of the lizard as an endangered species, which would come with environmental restrictions that opponents said would inflict serious economic damage on a region described as the nation’s top oil producer.
Lacking wildlife expertise in the state’s chief tax agency, Combs then contracted with a division of Texas A&M University — the Texas AgriLife Extension Service — in November 2011. But A&M needed help on the ground, so it sent out a request for proposal for a contractor that could handle contacts with landowners and oil companies who would sign up for the voluntary program and undertake measures to save the lizard — like cutting down mesquite and removing old oil equipment.
Officials say no one responded to the contracting request. TXOGA then went to Combs and floated a plan to have the oil and gas lobby group start up a nonprofit foundation to implement the Texas Conservation Plan in the lizard’s oil-rich habitat in the Permian Basin, according to TXOGA lobbyist and foundation board member Deb Hastings.
“We did have a conversation with the comptroller’s office to see if it would be appropriate if we set up a foundation temporarily,” Hastings said. She said she did not recall that Combs raised any objections.
The foundation was formed in February 2012 with three registered TXOGA lobbyists overseeing it as board members: Hastings, Robert Looney and Mari Ruckel.
When asked if anyone ever thought putting oil lobbyists in charge of lizard protection in an area dependent on the industry might present a conflict of interest, Hastings said: “I could see where there was some perception risk regarding that, but there was nothing nefarious about this. It was above board. It was meant to ensure the species was not listed.” Hastings emphasized that the foundation hired a wildlife biologist to handle the scientific oversight and run the day-to-day operations.
U.S. Fish and Wildlife withdrew its proposal to list the lizard last summer, but could reinstate it if voluntary efforts fail.
Lesli Gray, spokeswoman for the federal agency, said the officials gathered in Midland this month with counterparts from Texas A&M and the comptroller's office. She also said the comptroller's office has been providing regular updates as required in its state-federal conservation agreement.
"The comptroller is very pleased that the work done by all of the stakeholders involved in this process resulted in a plan that caused the U.S. Fish and Wildlife Service not to list the DSL," said Combs spokesman Lauren Willis. "We are proud of the role we played in that process and the work we did to save the West Texas oil and gas economy."
But some powerful Republican lawmakers are voicing concerns about TXOGA's role and the comptroller's oversight of endangered species. Chief among them is Sen. Kel Seliger, R-Amarillo, whose district includes much of the Permian Basin and the lizard’s habitat.
Seliger said independent oil companies are upset that TXOGA, which represents the interests of giants Exxon, Chevron and others, would be in charge of mitigation efforts for the whole industry — and potentially stacking the deck in favor of itself.
"You might have competitors determining costs that other competitors would have to incur to drill oil wells," he said.
More broadly, Seliger said there is no reason why the state comptroller should be in charge of coordinating the response to endangered species. He has a bill that would move that authority — which includes the right to hold the federal permit Combs now has at the comptroller’s office — to Texas Parks and Wildlife. An oversight board composed of several state agencies, including the comptroller’s office, is included in the latest version of the legislation, he said.
Willis, the Combs spokeswoman, said the comptroller is leaving the matter to the Legislature, but Seliger said the pressure against the legislation has been intense. He said Combs, TXOGA and the major oil companies were all trying to kill it.
“The comptroller and the majors are lobbying vigorously against it,” Seliger said. Rep. Dennis Bonnen, R-Angleton, who is carrying the legislation in the House, said oil industry opponents are trying to “threaten” members who dare support the effort to give oversight authority over endangered species listings to another agency.
For its part, TXOGA is poised to step out of direct involvement by handing over its authority to other board members. But the current board got to select the new one, and it has already identified its incoming chairman: Chisum, who sponsored the TXOGA-backed bill giving Combs the authority to handle endangered species matters.
Now an oil and gas lobbyist himself, Chisum tapped two others to join him — biochemist Glenna Kyle and Joe Maley of the Texas Agricultural Land Trust, TXOGA officials said.
Chisum was asked to respond to complaints that oil company interests shouldn't be in charge of the foundation set up to enact the conservation plan. He said qualified biologists are hired to do the work, but noted oil companies were paying to participate in the voluntary plan. Chisum said they should have a say in how it's implemented.
“It’s our money," he said.

industry_corpus2: Petrochemicals


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Our "TamilBrands" web platform aims to support farmers, cattle rearers and small scale manufacturers by bringing them to the visibility of people around the globe and to promote their products through digital marketing and other promotion strategies, to reach the market by the best supply chain strategies for the maximum profitability for producers as well as consumers.
To empower Tamil nadu made small scale manufactured products,cultural and traditional goods, cattle produce, farm produce, agricultural products, organic products to make meaningful difference in the market with their own brand identity.
Why to Support Tamil Brands?
1. All products are from Genuine Small Scale Producers.
2. Best Quality Products made by Small Scale Cottage Industries.
3. Chemical Free Food Products.
4. Legendary Customer Support Experience.
Recognition for Tamil Brands Initiatives from India's No.1 Leading E-Magazine .

industry_corpus2: Agriculture & Fisheries


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The Industrial Technical Learning Center is operated by the Inland Empire Regional Training Consortium which includes multiple partners, and sponsors. The Consortium was initially funded by The Trade Adjustment Assistance Community College and Career Training (TAACCCT grant).
Studies conducted by the Inland Empire Center of Excellence (COE) examined the 2014 median annual salary of individuals in San Bernardino and Riverside Counties employed in advanced manufacturing occupations. Across the five focus areas, the 2014 median annual income was approximately $39,031. In contrast, the 2014 median annual salary of generally skilled laborers in the same two-county region was approximately $27,000.
Applying a conservative 2% cost-of-living adjustment to the annual salaries of generally skilled laborers and individuals employed in the five TAACCCT focus areas, over the span of an average work life (25 years), it is projected that prospective TAACCCT-trained employees stand to earn approximately $393,096 more than their generally skilled laborer counterparts. Over the four-year TAACCCT project period, it is estimated that 2,589 workers and other adults will be served. Applying conservative employment projections to this population (2.7% annual job growth in advanced manufacturing occupations through industry growth and/or replacement over the next ten years; TAACCCT-trained employees remaining employed for 20 years), the long-term economic impact of the TAACCCT grant on the Inland Empire would minimally equate to approximately $168 million ($8.4 million annually).
While conservative employment projections have been identified, recent regional data suggests burgeoning employment opportunities for TAACCCT-trained employees in advance manufacturing fields. The Inland Empire Center of Excellence (COE) has identified 4,350 advanced manufacturing businesses within San Bernardino and Riverside Counties. In 2012, these businesses generated $24 billion in revenue and provided an estimated 96,519 jobs in the Inland Empire’s two-county region. The COE has identified 45 manufacturing occupations in San Bernardino and Riverside Counties that are expected to generate 2,020 annual openings (new and replacement jobs) over the next year alone. Furthermore, these projections do not take into account the “greying” of the current advanced manufacturing workforce. Over 90% of local advanced manufacturing employers anticipate growth and/or hiring to meet the expected workforce demand.
 Centers of Excellence. (2014). Advanced Manufacturing Industry & Occupations in the Inland Empire.


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Hey OCmoho, I'm willing to do it again but only if you promise to use a controller for the part where we have to drive over the broken debris. I can't drive vehicles with the XIM2, I'm forced to drive with the controller because of how Halo 3 works. When we turn with the joystick it sends signal that the joystick is being held at maximum near the deadzone so we get maximum turn speed. When we turn with the XIM2, there is no holding with the mouse because we don't hold anything down with the mouse. We just move the mouse left and right, so I'm guessing this is what causes the slow turning speed in Halo 3 with a mouse.
Sure, ill have my wireless controller handy, and i can switch to it when we get to the ghosts.
will you be available tonight?
For me mouse is better with everything but the chaingun mounted on the back of Warthogs. With those the Y-axis is overly sensitive when compared to the X-axis.
Yup, that is very annoying for me.
I should be on later If we want to try it.
I'll be able to participate during the next few hours if you are planning on trying tonight/this morning. I might be able to bring another along if there aren't enough players, but I can't guarantee they will be up as late as myself.
sounds good, im on now, matchmaking to see if anyone else wants to join us..
Well, I'll be hanging around on the title screen. Just send a message or an invite whenever you're ready to start setting up the game. I'll probably go offline around 1000 GMT if we don't get enough players before that time.
I guess we can try for tonight then.
What time zone? I'm in PST.
Well I'm EST and I believe ocmoho is MST.
We really need to find a decent time to get everyone together for it.
I can do it today or tomorrow.
I guess we can try both days if one of them doesn't work out.
I have it now, so I don't need to get it any more thanks guys for the help.

industry_corpus2: Gaming


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Radisson Hospitality AB, publicly listed on Nasdaq Stockholm, Sweden and part of the Radisson Hotel Group, is proud to announce the introduction of the Radisson hotel brand to Southern Europe with the signing of the Radisson Larnaca Beach Resort on the island of Cyprus – due to open in Q3 2019.
The new Radisson Larnaca Beach Resort is the group’s third hotel in Cyprus, and will complement the recently opened Radisson Blu Hotel, Larnaca. A year-round destination, Cyprus is a major tourist destination in the Eastern Mediterranean and is an island rich in history and culture – attracting more than two million tourists annually, while appealing to a wide range of travelers.
Radisson will bring its upscale, full-service hotel concept that delivers Scandinavian-inspired hospitality to Larnaca – a resort that will play a key role in the group’s growth across Southern Europe, the Middle East and Africa.
After an intensive refurbishment, the Radisson Larnaca Beach Resort will bring the brilliant essentials of the Radisson brand to life across 202 elegantly designed rooms – with ocean and garden views promising truly memorable experiences. The hotel will feature three restaurants (including a beach bar and restaurant), lounge bars, and a range of fitness and leisure facilities – as well as conference and meeting rooms.

industry_corpus2: Hospitality & Catering


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- Specially designed for Trials and BMX, these shin guards are ideal to avoid leg damage when the pedal slips.
- The main update consists on the use of a new foam material called D30, which is lightweight, flexible and comfortable. However, when an shock load is applied, it's able to absorb the impact, recovering its initial shape instantly.
- Furthermore, it features updated technical lycra and mesh fabric to guarantee a perfect fit and optimal riding comfort.
-These shin guards feature the socket-type fitting, so that straps and fastenings are no longer needed, which increases comfort and helps save weight.
- A foam and a drilled plastic (to save a good few grams) make for the protection system, which is easily removable and washable.
- Two sizes available: S(27cm long) and L (32cm long).
- Black with white NEON logo.


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Healthcare has been one of the key topics in the news and in our lives for much of the past decade. Healthcare systems have been focusing on how to better serve our communities resulting in many changes in the way care delivered and in creating greater access to it. We had the opportunity to look at three programs that are both successful and effective at achieving better delivery and access to care for our communities. As part of the 2014 Destination Swedish fundraising luncheon we created a video that highlights the Ballard Teen Health Clinic in Ballard High School, the incredible family residency program that trains new doctors, and the Swedish Community Specialty Care Clinic that provides high-quality specialized treatment and medical services to those who have no access to those services. These innovative solutions for healthier communities have had great impact for our youth, families, and the most vulnerable in our communities. We are excited that the event raised $920,000 to keep these vital programs funded.
Visit the Swedish Medical Center Foundation’s Innovative Solutions for Healthier Communities page to watch the video and learn more.

industry_corpus2: Health & Medicine


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The country’s banking sector seems to be showing signs of recovery as deposits have increased for two consecutive months following a drop from the latter part of 2018, the Summary of Economic and Financial Data has revealed.
The data, which was published by the Bank of Ghana, show that banks’ total deposits increased to GH¢71.9billion in February 2019 from GH¢70.5billion the previous month – translating into a 20 percent increment, the highest since October last year when it increased by 20.8 percent.
Compared to the same period last year (February 2018), banks’ deposits were GH¢59.9billion – which is 7.4 percent lower growth than recorded this time around.
Banks’ deposits as of the end of 2018 was GH¢68.3billion – a dip in annual growth rate to 17.4 percent from the 18.4 percent recorded in November. This some financial analysts blamed on what they called a ‘radical’ approach by the central bank to clean up the banking sector, which led to the revocation of five banks’ licences – triggering many panic-withdrawals across the country.
The 2019 rebound in deposits growth, a Professor of Economics at the University of Ghana – Prof. Peter Quartey said, can be rightly attributed to the banking sector reforms undertaken by the Bank of Ghana last year.
“Given the reform that banks have to recapitalise; given the reform that a director of a bank’s board has to be screened; given the reform on how loans should be advanced and several directives from the central bank, we see depositors building confidence in the existing banking institutions.
“Some have even moved their funds from microfinance and other financial institutions to formalised banking institutions. So yes, confidence has increased; but it has increased more in the banking sector than other financial institutions, especially microfinance institutions,” he said in an interview with the B&FT.
Following the successful clean-up of the banking sector, albeit it having consequences on the economy – namely job-losses, panic-withdrawals, and ultimately a GH¢12billion cost to taxpayers for the exercise – the central bank has said its next stop is the microfinance sector by end of June this year.
The clean-up in the sector, Governor of the Bank of Ghana Dr. Ernest Addison said, will cost the economy some GH¢700million.
“We have already announced that it will be the next phase, and we will be focusing on ways to see that depositors in that sector of the market are taken care of. We are working with the Ministry of Finance to raise the necessary resources to do that. I cannot tell you the exact date because it is yet to be decided, but the commitment is there.
“I can assure you that we are in the second quarter, and hopefully within this quarter we will be able to bring that issue to a conclusion because we are close to obtaining the resources we need to deal with microfinance institutions. The preliminary estimate that we have for microfinance institutions is just GH¢700million,” Dr. Addison said.


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Time to get your home tested for Radon, but don't know where to start? Finding qualified Radon professionals can be difficult, but we've put together a list of Cleveland, WI contractors to help you save time.
Click the link below to search for Cleveland, WI radon mitigation contractors.
Click the link below to search for Cleveland, WI radon testing contractors.
Cleveland, WI resides in a county which has been assigned a moderate risk zone by the EPA. It is recommended your home business or be tested for elevated levels for radon. Radon levels in the 53015 zip code have also been given a moderate assessment.
Cleveland, WI and the 53015 zip code are located in Manitowoc County, which has an EPA assigned Radon Zone of 2. A radon zone of 2 predicts an average indoor radon screening level between 2 and 4 pCi/L, which is within the recommended levels assigned by the EPA. Cleveland is located in a moderate risk area of the country. However, with any household or business, regardless of Radon Zone, it is suggested your home be tested for unsafe levels of radon.


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Ask someone to name every dimension they know of and they’ll likely list the following: length, width, and depth. They might also add time if they’re thinking outside the three-dimensional box. But asking a string theorist, “How many dimensions are there?” would elicit a very different response. According to this branch of theoretical physics, there are at least 10 dimensions of space, most of which are impossible for humans to perceive.
Dimensions are the metrics that physicists use to describe reality. Sounds broad, right? Let’s start with the three dimensions most people learn in grade school. The spatial dimensions—width, height, and depth—are the easiest to visualize. A horizontal line exists in one dimension because it only has length; a square is two-dimensional because it has length and width. Add depth and we get a cube, or a three-dimensional shape.
These three coordinates are used to pinpoint an object’s location in space. But space isn’t the only plane we exist on; we also exist in time, which is where the fourth dimension comes in. Once we know a dot’s altitude, longitude, latitude, and position in time, we have the tools needed to plot its existence in the universe as we know it.
But some physicists who subscribe to string theory argue there’s more to reality than the observable universe. String theory, also known as “superstring theory,” aims to unify two main theories describing how the universe works: general relativity (which applies to very large objects) and quantum mechanics (which applies to very small ones). In a four-dimensional universe, this theory wouldn’t be possible, but once scientists tweaked the math to include 10 dimensions—11 including time—their equations worked.
After coming up with a theory that hinges on the existence of 10 space dimensions, string theorists then had the job of explaining where those new dimensions were hiding. Their answer: They are just as real as the “big” dimensions we can see, but the extra dimensions are curled up so tightly that they’re too small for us to notice directly.
Our basic understanding of physics makes this hard to process, but string theorist Brian Greene does a great job of framing the concept in terms most people can understand. In his 2005 TED Talk, Greene compares these invisible dimensions to the cables connected to telephone poles: From a window, a wire looks like a one-dimensional line. But if we were to study it up close we’d see that the cord is actually round, making it three-dimensional. No analogy comparing unobservable dimensions to objects in the observable world can ever be perfect, but this illustrates how something so fundamental to reality could be hiding in plain sight.
String theory states there must be at least 10 dimensions of space plus one dimension for time, but there are physicists who argue that there are more. Some posit a universe composed of 11 space dimensions. But to really blow someone’s mind when they ask how many dimensions there are, say 26: That’s the magic number according to Bosonic string theory, and it’s as high as mainstream physicists are willing to go for the time being.

industry_corpus2: Technology & Research


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At Rocky Mountain Granite, Inc., we pride ourselves on our vast experience and affordable prices. We want to be your top choice in the Cody, Wyoming area for your Tile & Ceramic Products or Services needs. Please visit our Cody, Wyoming location today or call us directly at 307-587-4162.
If you have questions about our Tile & Ceramic products or services or would like to schedule an appointment, please contact us by filling out the form shown below. Thank you for visiting us at Rocky Mountain Granite, Inc. We look forward to serving you!

industry_corpus2: Real Estate & Construction


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Swift Ceiling Fan Wiring is going to be there for your goals regarding Ceiling Fan Wiring in Appleton, WI. Our company has a team of experienced experts and the most resourceful technologies around to supply exactly what you want. We are going to work with superior quality products and money saving practices to be certain that you will get the most effective solutions at the best price. We will make it easier to make decisions for your own work, address the questions you have, and prepare a meeting with our contractors when you give us a call at 844-233-9833.
You have a spending budget to comply with, and you need to cut costs. But, lowering costs shouldn't mean you lose excellent quality with Ceiling Fan Wiring in Appleton, WI. We provide you with the highest quality while still saving you money. We utilize the leading solutions and materials to make sure that the project will tolerate the test of time, and we save you money in ways which do not affect the quality for your job. We're able to accomplish this by offering you the best discounts in the market and steering clear of pricey errors. Save time and funds through calling Swift Ceiling Fan Wiring now. We're waiting to accept your call at 844-233-9833.
Ceiling Fan Wiring are available in Appleton, WI.
To come up with the best choices for Ceiling Fan Wiring in Appleton, WI, you've got to be kept informed. We ensure that you understand what can be expected. You will not deal with any sort of unexpected situations whenever you use Swift Ceiling Fan Wiring. You can start by discussing your project with our customer support representatives when you call 844-233-9833. During this phone call, you will get your concerns resolved, and we will schedule a time to get started with the work. We work with you throughout the entire project, and our team is going to show up on time and ready.
If you find yourself preparing a project for Ceiling Fan Wiring in Appleton, WI, there's lots of reasons to call Swift Ceiling Fan Wiring. We offer the top customer support ratings, the very best quality supplies, and the most sensible and productive cash saving solutions. We understand your needs and ambitions, and we are available to serve you with our experience. Call 844-233-9833 to connect with Swift Ceiling Fan Wiring and review your expectations regarding Ceiling Fan Wiring in Appleton.


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HEC 101, 102 | TESTIMA, spol. s r.o.
HEC-100 series of eddy current electrical conductivity meters, which are designed for quick & convenient measurement of material property, such as material separate, quality control, material state check and so on. The products use the electromagnetism testing principle, can testing objects focus on non-ferromagnetic materials.

industry_corpus2: Power & Energy


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Harmony Wright runs the day-to-day administrative operations at Seiniger Law.
Harmony has a Bachelor of Science degree in Psychology from Boise State University and an Associate of Science degree in Enology & Viticulture from Walla Walla Community College.
An avid foodie and gardener, Harmony enjoys cultivating heirloom vegetables, which her husband (a former chef) incorporates in their dinners together. She also spends time with her dog, Bowie, who likes chasing squirrels.
Harmony remains in the wine industry as the wine director for a local restaurant and continues to make wine as a hobby from the Cabernet Franc grapes she grows at home.


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I’m a classically trained musician who stopped playing quite as much classical music after discovering electronic music. I perform layered compositions with live loops, chiptunes, classical saxophone, and circuit bent toys. I’ve been fortunate to perform for such varied venues as art centers, rock venues, hacker spaces, warehouse parties, the Burning Man festival, and a SubGenius devival. As a composer and sound designer, I’ve created for theater, film, multi-channel installation, and community art events.
Here are a few sample tracks from my 2008 album All Of This Is Temporary. If you still like physical media, donate any amount and I’ll send you a copy.
You can also find it on iTunes, cd baby, or stream it on Pandora.
Mashups are fun. I want to make more of them. If you have good stem sources, let me know!
Low Orbit was a collaboration with Lorren Stafford. I have him to thank for bringing both chiptunes and circuit bending into my life.
Zurround was an ensemble that played live, improvisational electronic music. It existed in many different forms between 1995 – 2002, and played varied venues including both First Avenue’s Mainstage and 7th Street Entry, and a devival for the Church of the Subgenius. Signature sounds included Zharachne’s beat-poetry inspired lyrics; live saxophone, bass guitar, and effects mixing; and a lot of what we affectionately call “space drool” from one of its many synthesizers. Zurround introduced me to my love of synthesizers, and a short list included in its sound over the years include the Sequential Circuits Prophet 600, a Roland Juno 106, Roland JD800, Kurzweil K2000, Ensoniq ASR-10, and Doepfer A-100 modular. Members included myself, Nick Elmquist, Brian Etchison, Scott Keever, Jj Kidder, and Zharachne Rahkonen.

industry_corpus2: Film & Entertainment


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Donate your time to the Momentum mission!
Momentum is always in need of volunteers for our various events, programs, and day-to-day activities. If you are interested in serving the Birmingham community alongside Momentum, then fill out the following form. Be sure to list your volunteer interest and skills!

industry_corpus2: Others


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Follow Mothball, an adorable wombat, as she goes about her week sleeping, eating, scratching, digging holes and training humans to give her food on demand.
Diary of a Wombat is a highly entertaining book. It’s brief, simple text and hilarious illustrations encourage children to make inferences about the story. Children enjoy comparing Mothball’s point of view with what the humans probably thought about all of Mothball’s antics. Diary of a Wombat is written in past tense and contains repetition of a range of irregular past tense verbs, such as ate, slept and dug.
For further speech and language targets in Diary of a Wombat, see the list below.

industry_corpus2: Subject Education


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General terms and conditions: A written quotation accompanied by our standard terms and conditions will be provided at the start of any contract for works.
Work Guarantees: All works guaranteed for 12 months from date of completion, this covers parts and labour. Your statutory rights are not affected by our guarantee.
Complaints: Complaints can be made by contacting Michael Adams at the above address.


text:
This document sets out the terms and conditions for purchase of your Holiday at an ATPM Holiday Park by instalments under a Payment Plan. By proceeding with your booking, you confirm that you have read and acknowledge these Terms and Conditions.
The Agreement will start when all necessary details in the Purchase Pages have been completed and provided to Us, the Payment Plan Contract has been entered into between the Purchaser and Us by the Purchaser ticking (or directing us to) the box in the Purchase Pages authorising Us to charge their credit card.
provided that at least 2 payments, in addition to your deposit, can be made under any Payment Plan option before the first day of the Holiday.
You may select the frequency of repayments under your Payment Plan on the Purchase Pages.
Repayment options can be made weekly, fortnight or monthly, subject to the time frame between the date of your Holiday and the date you start your Payment Plan.
For the monthly Payment Plan, on the Start Date and monthly same date after that (Direct Debit Date).
The final payment for all Payment Plan options will be due 7 days before the date of the Holiday.
The final payment amount and final payment due date will be specified in the Purchase Pages.
Any outstanding or missed instalment under a Payment Plan must be paid on or before the final payment, on the date which is 7 days before the date of the Holiday.
The amount of each repayment or instalment due and payable by you under the Payment Plan will be as specified in the Purchase Pages.
All payments due to Us will be collected by Us in accordance with the terms of the Agreement.
All payments are in Australian dollars. The Purchaser is solely liable for any currency conversion fee charged.
you will not be entitled to a refund, subject to any statutory rights.
Please note: Once accepting a frequency for payment, the payment dates are fixed/automated and unable to be altered.
To cancel Payment Plan (prior to the final Direct Debit Date) you will need to contact us in writing and confirm your cancellation no less than 5 business days from your next Direct Debit Date. If you do not provide sufficient time for cancellation, we may be unable to cancel your Payment Plan prior to the next payment due date.
You must provide us with accurate and complete billing information including your legal name, address, telephone number, email address and in some cases, date of birth or other proof of identification. We will not be liable for any billing errors that occur as a result of you providing inaccurate billing information.
You must notify us immediately if your credit details provided to us for the purposes of charging your Payment Plan is no longer current or has changed. You can update your payment details by contacting the Holiday ParkHol.
We reserve the right to cancel your Payment Plan arrangement should two or more of your debit payments be returned or dishonoured. You are liable for any bank fees or merchant fees associated with dishonoured payments.
The biller name on your credit card statement will be the name of the Holiday Park where you have booked your Holiday.
If a payment is returned or dishonoured, you will be required to pay the missed payment by credit card before the Holiday.
If a debit payment falls due on any day which is not a business day, the payment will be made on the next business or calendar day. If you are unsure when the debit will be processed to your credit card, you should ask your financial institution.
It is your responsibility to have sufficient funds available on your credit card balance to enable your payments to be made.
If your credit card payment is declined is unsuccessful, we will use reasonable endeavours to notify you by text message, email or telephone that an amount is overdue. If the amount outstanding is not immediately paid, then we reserve the right to debit your credit card again after 3 business days.
Any queries concerning disputed debit payments must be directed to us in the first instance by contacting the holiday park. If we cannot resolve a query or dispute between us, you may refer your query or dispute to our bank who may ask you to provide information in connection with your query or dispute.
Except to the extent that disclosure is necessary in order to process credit card payments, investigate and resolve disputed transactions or is otherwise required by law, we will keep details of your credit card payments confidential.
Despite anything contained in these Terms and Conditions, the Australian Consumer Law (ACL) gives you statutory rights including guarantees and remedies that cannot be excluded or modified by these Terms and Conditions. The ACL guarantees and remedies include (depending on the type of failure, fault, or defect) repair or replacement, a refund, compensation for reasonably foreseeable loss or damage, or a resupply of the goods or services if the goods or services do not meet the standards required by the ACL. These Terms and Conditions do not purport to exclude any statutory rights available to you and must in all cases be read subject to those statutory provisions.
The Agreement may be terminated by Us at any time by notice in writing to you, if the Payment Plan has not been paid when due or you breach these Terms and Conditions.
Any notice required to be given by a party under the Agreement must be given in accordance with the particulars set out in the Purchase Pages or at the end hereof or as subsequently varied by notice.
keep your email account and mobile phone secure to protect the privacy of your personal and any credit information.
You are bound by the latest version of these Terms and Conditions. We will use reasonable endeavours to notify you of any changes to the Terms and Conditions by placing a notice on our website. Where there are material changes to these Terms and Conditions that could adversely affect or limit your rights under these Terms and Conditions, we will provide additional notice to you by way of the address or email address you have provided to Us. Where possible, we will give at least one month’s notice of such changes.
Australian Tourist Park Management is a member of the National Roads and Motorists’ Association Limited (ACN 000 010 506) (NRMA)* group of companies.
The Agreement is governed by the laws in force in the State of Queensland, Australia.
Telephone on – 07 5607 1405. If calling from outside of Australia +61 7 5607 1405.
*Insurance Australia Limited (trading as NRMA Insurance) and its related entities are separate and unrelated to National Roads and Motorists’ Association Limited.
“Day” means any business day in Queensland, Australia.
“Direct Debit Date” means the date when each payment is to be deducted in accordance with these Terms and Conditions.
Holiday means the booking of accommodation at one of the Holiday Parks which are owned or managed by ATPM.
“Payment Plan Period” means the period from the Start Date to the Day which is 7 days before the date of the Holiday.
“Personal Information” has the meaning ascribed to it by the Privacy Act 1988.
“Purchase Pages” means those pages on our website headed “Book Online”, “Check Availability”, “Booking Details”, “Membership Details” and “Checkout”.
“Purchaser” or “you” means the person whose identity is inserted in the applicable section of the Purchase Pages, whose name must also be on the credit card used for the Payment Plan. The word “Your” has a corresponding meaning.
“Terms and Conditions” means the terms and conditions in this document which form part of the Agreement regarding your Payment Plan.
“We, Us or “ATPM” means Australian Tourist Park Management, management company of Macleay Valley Coast Holiday Parks. ACN 061 270 513 of Suite L218A, Level 2 The Strand at Coolangatta 72-80, Marine Parade, Coolangatta QLD 4225. The word “Our” has a corresponding meaning.

industry_corpus2: Travel & Geography


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We gather and utilize various types of information listed below. By using this Site, or by continuing your membership with www.KittyKickStix.com, you signify your acceptance of this Policy. Note that this Policy applies only with respect to the information collected by www.KittyKickStix.com and not any information collected or obtained through other methods or sources.
Automatic: Automatic information is information that we collect that is not personally identifiable such as your IP address, site usage and purchase behavior, browser type, browser activity, and browser settings.
information by them. Additionally, you agree that we may use and disclose all such information so submitted to such third parties in the same manner in which we are entitled to use and disclose any other information you submit to us.
By submitting photographic images to KittyKickStix, you grant KittyKickStix a perpetual, royalty-free license to use, reproduce, modify, publish, distribute, and otherwise exercise all copyright and publicity rights with respect to those photographic images at its sole discretion, including storing it on KittyKickStix servers and incorporating it in other works in any media now known or later developed including, without limitation, published books. KittyKickStix reserves the right to select, edit and arrange submissions, and to remove images from the KittyKickStix website at any time at its sole discretion.
When you enter your information, you will automatically be registered to receive promotional offers and updates, via e-mails, from www.KittyKickStix.com and from the Network Sites and other associated e-mail brands and considered a ‘Member’.
Additionally, when you become a Member, you will be provided with the opportunity to receive promotional offers, via e-mails, from partners of www.KittyKickStix.com. While some of these opportunities will only be sent to you if you expressly request them, others may be sent to you unless you elect not to receive them. Accordingly, please review these offers carefully.
Members may, at any time, choose not to receive promotional e-mails from www.KittyKickStix.com, the Network Sites or partners of www.KittyKickStix.com by following the “unsubscribe” instructions in the applicable e-mail. Notwithstanding the foregoing, www.KittyKickStix.com may continue to contact Members for the purpose of communicating information about their membership with www.KittyKickStix.com to Members, or similar information relating to www.KittyKickStix.com, the Site or your membership, as well as to facilitate, complete or confirm any transaction that Members’ enter into or in response to or fulfillment of Members’ inquiries or requests.
Once the cat toy has been shipped, all orders are final.


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WT1 is the ultimate replacement for all bitumen based roof membrane with excellent adhesion to brick, stone, concrete, polyester, lead, metals and plastics.
INTRODUCING... WT1 - Waterproofing Technology No.1 REPAIR WATERPROOF SEAL WT1 is the ultimate replacement for all bitumen based roof membrane with excellent adhesion to brick, stone, concrete, polyester, lead, metals and plastics. WT1 is a complete new formulated compound with a combined polymer and polyurethane union, which forms a 100% waterproof membrane and remains stable with weather fluctuations, without shrinking or cracking. It is ideal for the quick repair of flat and sloping roofs, and for tanking, with one application straight from the container. It is also used on concrete terraces, balconies and floors, and under ideal conditions, can be rendered or plastered. WT1 is compatible with the C-TEC adhesive range, CT1 and Power Grab ‘n’ Bond, therefore allowing attachment of suitable substrates such as decking products or tiles.


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How many squares on a chess board?
How many squares are there on a chess board? Depending upon your interpretation, this can be perceived as a trick question. The answer of 64 squares (8×8), is perfectly valid, but there is also an alternative answer if we count the squares of different sizes, not just the individual squares.
There's also a formula for quickly calculating the sum of squares. For a chess board, with n=8, we can see the sum is 204.
Interestingly, as n gets larger, this formula tends to n3/3. I'm sure there is some particularly cool consequence of this, but I can't think of one at the moment. If you think of one, drop me a note, and I'll update this page and give you credit!
"A consequence of the sum of n2 tending to n3/3. It turns out to be quite simple and fascinating! Consider each number n2 to correspond to n2 little cubes of size 1, put in such way to form a square. For each n=1,2,3,… let us put this squares on top of each other (no need to centre them, thanks to Fubini's theorem). If we repeat this process infinitely, we can actually 'see' a pyramid forming, whose volume is indeed n3/3 = the sum of the cubes volume!"
I found a picture of such a Ziggurat, on the internet, made from sugar cubes!
How about the number of rectangles on a chess board? Well, to make a rectangle you need to pick any two of the vertical lines, and any two of the horizontal lines. There are 9C2 pairs of horizontal lines you can pick (36 distinct pairs), and the same number of vertical pairs, so the answer is 36×36=1,296.
Take an 18×18 grid of squares, and remove two of them so that the resulting figure contains exactly 2002 squares of all different sizes made from the remaining squares.
There's an answer on the internet, but I could not agree with it, so I wrote a bit of code to generate all the answers.
If you want to give it a go yourself, here's an applet below. In this variant, you can also specify different grid sizes and the number of shaded blocks you are allowed to set.
Did you find a solution? If you want to see all 64 solutions (not de-duplicated by rotations or reflections), click below.


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According to a report circulating via social media and the blogosphere, Steve Burns, former host of popular children’s TV show Blue’s Clues, has died in a car accident.
The report claims that the US entertainer was killed in a one-car crash in Pennsylvania.
However, the claims in the report are false. Steve Burns is not dead. There are no credible news sources that support the claims in the report.
I think the worst part about the latest rumor of my demise is that in it I was driving a Dodge Charger. Still arguably #alive, folks. Sorry.
In fact, Steve has been the subject of a number of death hoaxes over many years.
The false death report comes from a dodgy fake-news website called msmbc.com. This nasty clickbait website churns out a stream of ‘shocking’ and entirely fictional stories disguised as news. The fake news site tries to further the illusion of legitimacy by using a name very similar to the genuine news site msnbc.
The goal of the site’s owners is to trick as many people as possible into visiting and sharing its fake material, thereby increasing advertising revenue.
Nothing published on the website should be taken seriously. It is wise to check any social media reports that claim a celebrity has died before sharing them. If a famous person really does die, the news will be extensively covered by the mainstream media and should be easily verified via an online news search.
Steve Burns, 42, was killed in a one-car crash in Pennsylvania, a local coroner said Friday.
Burns was pronounced dead at 7:11 p.m. Friday at The Reading Hospital and Medical Center in Reading, Berks County Coroner Randall Wiseman told The Associated Press.


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Last winter (on March 4th) a terrible accident happened in the backcountry of Bostan. A couple of snowshoers got caught in an avalanche a few hundred meter above the mountain hut. This morning the avalanche risk was 4 and the slope they were traversing had an angle of about 35°. Fortunately the lady could free herself. Her husband, who was ahead of her, got taken away by the slab and buried under a few metres of snow. The rescuers (and the victims wife) were not able to localise the man, because he was not wearing an avalanche tranceiver. Sadly he was only found in the spring by a walker, when the snow had melted away the metres of snow that had been covering his body during the previous months.
Always bring your avalanche trinity; probe, shovel, transceiver.
Always inform yourself about the current avalanche risk, before you undertake any off piste or backcountry activity in snowy mountains.
Avalanche flags are only visible within the skiarea and don't give comprehensive information. The daily avalanche bulletin is much more useful. So I suggest you put this Meteo France link in your Safari or favourites list, so you can always open and consult it as long you have internet connection.
Strangly only written in French, the avalanche bulletin shows your choosen area with risk factors of 1-5 indicated. In the text the current risks and dangers for the area will be further explained.
Risk 3 (black and yellow blocks): Many slopes are suspicious and dangerous; be very sensible!
Risk 1 (yellow flag): The mountains are relatively safe, but remember that risk 0 does not exist (in winter).
I remember some people sharing their worried feelings last March, saying: “I told you that even hiking up to the Bostan hut is dangerous”.
Sorry, but I don't agree; It IS safe if you stick to the 4x4 track when you hike up to the Bostan hut. But if you leave this track and come closer to steep faces or if you climb further up after and above the hut, yes there is definately an avalanche danger and especially when there is current risk 3 or 4!
Be very careful to follow summer hiking trails in winter and following other peoples skin or snowshoe tracks in the backcountry. Don't act like a sheep; you should always ask yourself if this is todays safest option!
Make sure you always inform yourself about the current risk and base your decisions on it IF and where you want to go. Follow a course if you would like to learn more about interpreting the avalanche bulletin, or book a guide for your outing.
If you want to stay away from trouble, the 30° rule is the one to remember!
If you are not able to measure or estimate slope angles, you should consider a(n avalanche) course, or again; book a guide.
Recent and natural avalanche activity on similar slopes might be the 'best' warning signal you could get. Noticing these kind of signs and acting upon it, is crucial and could safe your life!
There are many more warning signals to notice in the backcountry; abundant snowfall, rising temperatures, whoompf sounds, shooting cracks, etc. To recognise and interpret them well, you should follow an advanced avalanche course. Or book a guide who will notice these warning signals for you to keep you safe.
I have written down these four straight forward recommendations to learn from the Bostan tragedy. But there are many more things to learn and consider, as avalanche knowledge is very complex. I am not an avalanche expert neither, I just have interest in the subject and like to share my ipinion with you. I am pretty sure that if you learn more about these 4 pointers and start using them, you will be already MUCH SAFER out there! And that is exactly my objective with this 2 blogpost.
On Wednesday 12 December I invite you for a 1 day training that deepens your basic knowledge around snowsafety. In the afternoon you will learn how to use your avalanche trinity and we will practice a rescue operation. Price €65,-pp incl. outdoor lunch. Please send me a message if you would like to join this day or if you would like to book a private trainingday for you and your own group?
Thanks for your attention, don't hesitate leaving a comment on this post on FB and above all: STAY SAFE!


text: elektromarkt.lt was registered 4 years 4 months ago. It has a alexa rank of #150,128 in the world. It is a domain having .lt extension. This site has a Google PageRank of 4/10. It is estimated worth of $ 45,600.00 and have a daily income of around $ 76.00. As no active threats were reported recently, elektromarkt.lt is SAFE to browse.

industry_corpus2: Computing & Telecommunications