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A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens
Roberto Rodriguez, Ryotaro Nakamura, Joycelynne M. Palmer, Pablo Parker, Sepideh Shayani, Auyaporn Nademanee, David Snyder, Vinod Pullarkat, Neil Kogut, Joseph Rosenthal, Eileen Smith, Chatchada Karanes, Margaret O'Donnell, Amrita Y. Krishnan, David Senitzer and Stephen J. Forman
Blood 2010 115:1098-1105; doi: https://doi.org/10.1182/blood-2009-03-207563
Department of Hematology/Hematopoietic Cell Transplantation,
Ryotaro Nakamura
Joycelynne M. Palmer
Division of Biostatistics, and
Pablo Parker
Sepideh Shayani
Department of Pharmacy, City of Hope National Medical Center, Duarte, CA; and
Auyaporn Nademanee
David Snyder
Vinod Pullarkat
Neil Kogut
City of Hope–Southern California Kaiser Permanente Bone Marrow Transplant Program, Duarte, CA
Joseph Rosenthal
Eileen Smith
Chatchada Karanes
Margaret O'Donnell
Amrita Y. Krishnan
David Senitzer
Stephen J. Forman
This article has an Erratum 115(21):4318
Combination tacrolimus and sirolimus graft-versus-host disease (GVHD) prophylaxis for allogeneic transplant in patients conditioned with a fractionated total body irradiation–based regimen has shown encouraging results. We studied this prophylaxis combination in 85 patients receiving a matched-sibling transplant conditioned with 3 different regimens:fludarabine-melphalan (n = 46); total body irradiation–etoposide (n = 28), and busulfan-cyclophosphamide (n = 11). The conditioning regimens were completed on day −4. Sirolimus and tacrolimus were started on day −3 to avoid overlap with conditioning therapy. All patients engrafted, with a median time to neutrophil engraftment of 15 days. The cumulative incidence of acute GVHD grades II to IV and III to IV was 43% and 19%, respectively, with no significant difference by conditioning regimen. The 2-year cumulative incidence of chronic GVHD was 46%. With a median follow-up of 26 months, disease-free survival was 58% and overall survival, 66%. The day-100 and 2-year nonrelapse mortality was 4.8% and 10.2%, respectively. The overall incidence of thrombotic microangiopathy was 19%, and it was significantly higher with busulfan/cyclophosphamide (55%, P = .005). Tacrolimus plus sirolimus is an effective combination for acute GVHD prophylaxis and is associated with very low nonrelapse mortality. Thrombotic microangiopathy is a significant complication with this regimen, particularly in patients receiving busulfan/cyclophosphamide.
Graft-versus-host disease (GVHD) remains one of the most challenging obstacles to successful allogeneic hematopoietic cell transplantation (HCT). Standard prophylactic regimens with tacrolimus/methotrexate or cyclosporine/methotrexate are associated with acute GVHD in close to half of sibling transplants.1
Sirolimus, originally named rapamycin, binds to the same family of intracellular FK-506 (tacrolimus)–binding proteins (FKBP12 and others) at a site distinct from tacrolimus. Sirolimus-FKBP complexes inhibit the mammalian target of rapamycin (mTOR), a kinase that regulates cell cycle entry in response to interleukin 2 (IL-2) signaling and other cellular functions. Cell cycle entry in the presence of sirolimus induces T-cell apoptosis, and deprivation of IL-2 signaling renders antigen-activated T cells unresponsive. Both mechanisms are thought to contribute to T-cell immunologic tolerance.2 Sirolimus has been widely used as an immunosuppressant in solid organ transplantation to prevent immune-mediated graft rejection3⇓–5 and has been evaluated for treatment of acute GVHD6 and chronic GVHD.7
Recently, the novel combination of tacrolimus and sirolimus was evaluated by researchers at the Dana-Farber Cancer Institute (DFCI) in a cohort of 30 patients who received matched-related peripheral blood stem cells and were conditioned with fractionated total body irradiation (TBI) and cyclophosphamide (Cy).8,9 The extended results of 53 matched-related HCTs were very promising in that the cumulative incidence of grade II to IV acute GVHD was 19%, and only 3 patients developed grade III to IV acute GVHD.9 The nonrelapse mortality (NRM) rates were also encouraging; the day-30 and day-100 rates were 0% and 5%, respectively.9 Another positive outcome, seen in this study and others, was that the use of sirolimus was found to be associated with reductions in cytomegalovirus (CMV) viremia10 and the incidence/severity of oral mucositis.11 However, sirolimus is associated with an increased risk of thrombotic microangiopathy (TMA), with a rate of 10.8% in the sirolimus group and 4.2% in the nonsirolimus group (odds ratio, 2.79, P = .03) in a retrospective analysis of myeloablative allogeneic HCT recipients.12 Another recent study showed an increase in veno-occlusive disease (VOD) associated with sirolimus use, particularly when methotrexate was added to the GVHD prophylaxis, or busulfan (Bu)/Cy was used in conditioning.13
Thus far data have been reported exclusively from DFCI except for a recent publication from the Fred Hutchinson Cancer Center (FHCC) evaluating sirolimus combined with either tacrolimus or cyclosporine in unrelated donor HCT (n = 26) with an unexpectedly high incidence of acute GVHD (77%).14 Due to toxicity, administration of sirolimus was discontinued earlier than planned in 11 patients, but after the onset of GVHD. Possible explanations for the discrepant results between DFCI and FHCC may include differential timing of immunosuppression, use of cyclosporine instead of tacrolimus in some cases, and use of Bu/Cy in some cases.
In this prospective pilot/phase II trial, conducted at City of Hope, we sought to determine the efficacy and safety of sirolimus combined with tacrolimus for 3 different conditioning regimens: fludarabine-melphalan (Flu/Mel), TBI-etoposide (TBI/VP16), and Bu/Cy. The secondary objectives of this study included an evaluation of risk factors associated with acute GVHD and TMA. This protocol extended the DFCI experience before the phase III trial sponsored by the Blood and Marrow Transplant Clinical Trial Network (BMT CTN). We designed the study to complete the conditioning regimen on day −4, before starting the immunosuppression on day −3 to prevent possible drug interactions between conditioning chemotherapeutic drugs and tacrolimus/sirolimus.
This phase II study, Institutional ReviewBoard 04052, was approved by the City of Hope Institutional ReviewBoard. The primary endpoints were toxicity (including TMA) and incidence/severity of acute GVHD; secondary endpoints included incidence of chronic GVHD and survival at 100 days, 1 year, and 2 years. Acute and chronic GVHD events were graded according to established criteria.15,16 Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0).17 TMA was defined as the simultaneous occurrence of schistocytosis, increased lactate dehydrogenase, and persistent thrombocytopenia (below 50 000/μL). Patients were eligible if they had a matched sibling donor and adequate organ function, defined as creatinine clearance more than 50 mL/minute, pulmonary diffusion capacity (DLCO) of more than 50%, and cardiac ejection fraction of more than 50%. Conditioning regimen selection followed City of Hope standard treatment/practice guidelines, using TBI/VP16 for patients younger than 50 years with acute leukemia in first or subsequent remission, Flu/Mel for patients older than 50 years or with comorbid conditions, and Bu/Cy for patients with myeloproliferative disorders in chronic phase or acute leukemia and myelodysplastic syndrome with contraindication to TBI. Peripheral stem cell donors were mobilized with granulocyte colony-stimulating factor 10 μg/kg for 4 days, to a targeted CD34+ cell dose of 2 to 5 × 106/kg. The day of stem cell infusion was defined as day 0. Neutrophil engraftment was defined as the first of 3 consecutive days with an absolute neutrophil count of 500 cells/μL.
GVHD prophylaxis
The GVHD prophylaxis was administered according to published reports,8 as follows: sirolimus 12 mg by mouth on day −3 (loading dose), followed by 4 mg orally daily, with the 4-mg dose being adjusted as necessary to maintain serum levels between 3 and 12 ng/mL by high performance liquid chromatography (HPLC); tacrolimus 0.02 mg/kg intravenously daily starting on day −3, switched to an equivalent oral dose when oral intake was adequate, to maintain target serum levels of 5 to 10 ng/mL. Tacrolimus and sirolimus levels were measured at least weekly until around day 100, and the dose was adjusted for the target levels and for clinical toxicity. Tapering of immunosuppression was to start around day 100; tapering was allowed earlier for relapsed malignancy.
Conditioning regimen
For TBI/VP16, 1320 cGy in 11 fractions was given from day −8 to day −5, followed by etoposide at 60 mg/kg of adjusted ideal body weight on day −4. For Flu/Mel, fludarabine was given intravenously at 25 mg/m2 per day for 5 days, from day −9 to day −5, and melphalan was given intravenously at 140 mg/m2 of adjusted ideal body weight on day −4. For Bu/Cy, busulfan was given intravenously at 0.8 mg/kg on day −10, and subsequently adjusted to an area under the curve of 800 to 1200, for a total of 16 doses every 6 hours from day −9 to day −6, and cyclophosphamide was given at 60 mg/kg/day of ideal body weight on days −5 and −4.
Supportive care, including prophylactic antibiotics, antifungal therapy, total parenteral nutrition, hematopoietic growth factors, immune globulin replacement, and treatment of mucositis and neutropenic fever, was administered in accordance with institutional standard practice guidelines.18 Choice of antifungal agent was at the discretion of the treating physician. Sixty-six patients received Abelcet at (1-2 mg/kg), 10 received micafungin, 9 received caspofungin, and 1 patient received itraconazole. Voriconazole was prohibited as a prophylactic drug. Monitoring for CMV viremia was performed twice a week from day +21 to day +100, using polymerase chain reaction and/or the shell vial method, and patients received preemptive ganciclovir at onset of CMV reactivation.
Overall survival (OS), disease-free survival (DFS), time to relapse, acute GVHD, and NRM rates were calculated using the product-limit method, and 95% confidence intervals were calculated using the logit transformation and the Greenwood variance estimate.19 Differences between survival curves were assessed by the log-rank test. When analyzing the prognostic significance of known/suspected risk factors on time to event variables (eg, OS, DFS, relapse, NRM, acute GVHD, and TMA), Cox regression was used.20 Factors evaluated for association with outcome included: patient age at transplantation, donor sex, sex combinations (female donor to male recipient vs others; and previously pregnant female donor with male recipient vs others), disease risk status at transplantation (based on disease features and disease status at transplantation), recipient CMV status, number of CD34+ cells infused (above or below median), and conditioning regimen (Flu/Mel vs TBI/VP16 vs Bu/Cy; and reduced intensity vs ablative). Acute GVHD (grade II to IV) was treated as a time-dependent covariate in the risk factor analysis for TMA. The cumulative incidence of acute GVHD and hazard ratio were estimated after taking into account the competing risk of death and relapse. Similarly, the cumulative incidence of TMA and hazard ratio were estimated after accounting for the competing risk of death and relapse. The cumulative incidence for relapse was also computed treating a nonrelapse death event as a competing risk.
Patient, disease, and treatment characteristics are shown in Table 1. The median age was 48 years (range, 10-67 years). Of the 85 patients treated, 3 (3.5%) were pediatric cases, under the age of 18 at the time of transplant. Most patients received peripheral stem cells (n = 80: 94%). The most common diagnoses were acute myeloid leukemia (39%) and acute lymphoblastic leukemia (21%). Low risk disease, defined as acute leukemia in first remission, chronic myelogenous leukemia in chronic phase, myeloproliferative disorders, and low-grade myelodysplastic syndrome (RA/RARS), was present in 54% of all cases. Disease characteristics stratified by conditioning regimen are shown in Table 2. The most commonly used regimen was Flu/Mel (54%), followed by TBI/VP16 (33%). The Bu/Cy arm was closed to accrual after a preplanned interim analysis of the first 11 patients showed a high rate of thrombotic microangiopathy (see "Toxicity/thrombotic microangiopathy" below); most of these patients had low-risk disease. Among the pediatric cases, 2 of 3 received an ablative regimen of TBI/VP16, and none of the pediatric patients was diagnosed with TMA or acute GVHD.
Patient characteristics (n = 85)
Diagnosis, remission status by conditioning regimen
Tacrolimus and sirolimus serum levels were measured at least weekly (twice a week in most cases) until around day 100. During the first 30 days after transplantation, 792 samples for tacrolimus and 606 samples for sirolimus were taken from 85 patients. Median sampling points during the first 30 days were 9 for tacrolimus (range, 4-12) and 7 for sirolimus (range, 4-10). Four of 85 patients had to discontinue tacrolimus and/or sirolimus early after HCT (before day +30) due to TMA/diffuse alveolar hemorrhage, mental status change, renal insufficiency, or TMA. We calculated median levels of tacrolimus and sirolimus for the first 30 days in each patient. The median (interquartile range, IQR) tacrolimus and sirolimus levels for all patients during the first 30 days were 9.2 ng/mL (IQR, 7.8, 10.3) and 7.2 ng/mL (IQR, 5.9, 8.9), respectively. While there were no significant differences in the sirolimus levels according to the 3 conditioning regimens, the tacrolimus levels were higher in Bu/Cy and TBI/VP16 compared with Flu/Mel (Table 3).
Median tacrolimus and sirolimus levels during the first 30 days after HCT
Engraftment and chimerism
All patients experienced neutrophil engraftment (absolute neutrophil count > 500) with a median time to engraftment of 15 days (range, 10-26 days). Chimerism of the day 30 bone marrow mononuclear cells by short tandem repeat analysis showed more than 90% donor in 90% of the patients.
GVHD
The probability of developing grade II to IV acute GVHD was 43% (95% CI, 37-50), with the median onset of 19 days (range, 3-89 days). Of the 34 patients who developed grade II to IV acute GVHD, 21 (25%) were grade II, 10 (12%) were grade III, and 3 (4%) were grade IV. Thirteen of 21 patients with grade II acute GVHD had mainly upper gastrointestinal (GI) involvement. Nine cases were diagnosed by histology from upper GI endoscopy (5 upper GI involvement only, 4 with both upper and lower GI tract involvement, but with limited diarrhea < 500 mL). Four cases without a biopsy had significant upper GI tract symptoms (nausea, vomiting, and anorexia), and either stage I to II skin, stage 0 liver (alanine aminotransferase/aspartate aminotransferase [ALT/AST] elevation), or stage 0 lower GI GVHD (mild diarrhea < 500 mL) for which steroids were started. In these 13 cases of mainly upper gastrointestinal GVHD, the median onset was 23 days (range, 11-85 days).
There was a higher probability of acute GVHD for patients conditioned with Bu/Cy compared with TBI/VP16 and Flu/Mel (64%, 49%, and 34%, respectively) without reaching statistical significance (P = .12; Figure 1). The probability of limited and extensive chronic GVHD was 51% (29% limited, 71% extensive).
Cumulative incidence of grade II to IV acute graft-versus-host disease according to conditioning.
With a median follow-up of 26 months (range, 14-37 months) for surviving patients, 55 of the 85 patients are alive. Twenty-two patients died of relapse, while 8 deaths were due to nonrelapse causes, including acute/chronic GVHD (3), multiorgan failure (1), mucormycosis (1), leukoencephalopathy (1), multifactorial respiratory failure developing after initial diffuse alveolar hemorrhage (1), and unknown cause without relapse (1). The probabilities of OS, DFS, and relapse at 2 years were 66% (CI, 59%-72%), 58% (CI, 52%-64%), and 34% (CI, 28%-42%), respectively. The day-100, 1-year, and 2-year NRM rates were 4.8% (CI, 2%-12%), 10.2% (CI, 6%-18%), and 10.2% (CI, 6%-18%), respectively. Conditioning regimen was not significantly associated with OS (Figure 2A), DFS, relapse, or NRM (Figure 2B).
Probabilities according to conditioning. Overall survival (A) and nonrelapse mortality (B).
Toxicity/thrombotic microangiopathy
Patients who experienced grade III or higher lung, liver, and TMA toxicity are summarized in Table 4 by conditioning regimen. Two cases of fatal alveolar hemorrhage were seen, 1 with Flu/Mel and 1 with TBI/VP16. Engraftment syndrome, characterized by fever, rash, and pulmonary infiltrates around the time of engraftment, was frequently observed with Flu/Mel (22%), but was reversible with corticosteroids in all cases. Liver toxicity (CTCAE v3.0, more than grade III) including VOD (n = 2) was seen more frequently with Bu/Cy (27%) than with TBI/VP16 (18%) or Flu/Mel (11%), without statistical significance (Table 4); all cases were reversible. The non-VOD liver toxicities were mostly elevated liver enzymes without clear GVHD and noted at the median onset of 23 days after HCT (range, day −4 to +76).
Lung, liver, TMA toxicities, grade more than III by regimen
TMA was a major complication that developed in 16 patients (19%). The median time to onset was 5 weeks after HCT (Figure 3A-B) and was found to be significantly associated with conditioning regimen (Table 4): Bu/Cy (55%) compared with TBI/VP16 (25%) and Flu/Mel (6.5%; P < .005). The Bu/Cy arm was closed to accrual early as a result of this finding. Twelve of 16 patients with TMA were also diagnosed with acute GVHD. GVHD preceded TMA in all of these cases. TMA was managed by holding tacrolimus in 50% of cases and/or holding sirolimus in 85% of cases; plasma exchange was performed in 1 case. Hemodialysis was required in 1 patient. TMA was reversible in all cases. The median levels (ng/mL) of tacrolimus and sirolimus at onset of TMA were 9.4 (range, 6.7-13.0) and 8.1 (range, 5.3-13.3), respectively, not significantly different from the median values for non-TMA patients over the first 30 days (tacrolimus: 9.1 [range, 3.5-13.4], P = .14; sirolimus: 7.2 [range, 2.5-18.8], P = .33). We further examined the effect of drug level on TMA risk using cut points at each quartile. Although TMA risk appeared to increase incrementally with increasing drug exposure by quartile analysis (Table 5), none of the cut point classifications (ie, quartiles; <, ≥ 25th percentile; median; <, ≥ 75th percentile) for tacrolimus or sirolimus were significantly associated with TMA risk. In addition, an examination of a possible threshold effect between serum level and onset of TMA was explored using the generalized estimating equation method. While the results of this analysis also showed no threshold effect, the results were difficult to estimate given the limited number of patients and TMA events.
Cumulative incidence with 95% confidence interval. Thrombotic microangiopathy (A) and stratified by conditioning (B).
Results of Cox univariate and multivariate analysis for TMA
CMV infection
CMV reactivation was observed in 16 of 64 patients (25%) who were seropositive. There were no cases of CMV disease (CMV pneumonia or gastrointestinal involvement).
Factors associated with outcome
Cox regression analysis was performed to identify potential factors (see "Statistical analysis" above) associated with survival, relapse, NRM, acute GVHD, and TMA. For the survival/relapse endpoints, the patient disease risk (high or low) was the primary factor significantly associated with OS, DFS, relapse risk, and NRM. In addition, tacrolimus/sirolimus levels over the first 30 days were included in the model in evaluating the risk factors for acute GVHD and TMA (Table 5). There were no significant factors found to predict acute GVHD in our analysis. Significant factors associated with increased TMA risk were conditioning regimen (patients conditioned with an ablative regimen, either TBI or Bu/Cy, had a 5-fold increase in risk) and prior acute GVHD (grade II-IV), which both remained significant in multivariate analysis (Table 5).
Based on encouraging phase II study data from DFCI,8,9 we prospectively tested the combination of tacrolimus and sirolimus as GVHD prophylaxis in patients undergoing HLA-matched sibling donor HCT conditioned with 3 different regimens. Administration of conditioning therapy and GVHD prophylaxis were nonoverlapping to avoid potential adverse interactions.
In our study, we observed a 43% rate of grade II to IV acute GVHD (grade III-IV, 19%). The data are at least comparable with our historic experience; the incidence of acute GVHD grade II to IV was approximately 50% in Flu/Mel conditioning using cyclosporine and micophenolate,21 and approximately 60% in full-intensity conditioning (TBI/VP, TBI/Cy, Bu/Cy) using cyclosporine and methorexate.22 The incidence of acute GVHD was lowest with Flu/Mel followed by TBI/VP16, and the highest in Bu/Cy, although the difference did not reach statistical significance (P = .12), as sample size for the Bu/Cy group was small due to early closure.
The DFCI experience with tacrolimus and sirolimus showed a lower cumulative incidence of grade II to IV acute GVHD of 19% using a conditioning regimen of cyclophosphamide followed by TBI,8,9 and 11% using the reduced intensity regimen of intravenous busulfan and fludarabine.23 The reason for the relatively higher rate of acute GVHD in this study is unknown. The patient characteristics in our study appear similar to those reported by DFCI. The difference may be partly attributable to different conditioning regimens used in our study (FTBI/Cy vs FTBI/VP16, Bu/Cy, and Flu/Mel). The FHCC recently published their experience using a calcineurin inhibitor with sirolimus and methotrexate for 26 high-risk patients receiving unrelated donor transplants, conditioned with TBI/Cy or Bu/Cy. A high incidence of grade II to IV acute GVHD of 77% led to the early discontinuation of the study.13 Suggested possible explanations for the discrepant results between DFCI and FHCC include different timing of immunosuppression, use of cyclosporine instead of tacrolimus in some cases, and use of Bu/Cy in some cases.24
Of clinical importance is the fact that severity of acute GVHD in our experience was generally mild; for example, approximately 60% of cases with grade II GVHD were mainly upper gastrointestinal, a form of GVHD that is known to have a relatively good prognosis.25 It has been recognized that conditioning-related injury of the upper GI tract can be clinically and histologically similar to upper gastrointestinal GVHD if diagnosed close to conditioning therapy. This may possibly explain the higher rate of acute GVHD in this study compared with DFCI results. Overall, 3 deaths (of 85 patients) were directly attributable to GVHD. When analyzed as a time-dependent variable, acute GVHD (grade II to IV) was not significantly associated with inferior OS or NRM in our cohort (data not shown). Chronic GVHD observed in our study was similar to the DFCI results.
Our survival data were very encouraging with a remarkably low NRM rate of 10% over 2-year follow-up across the 3 conditioning regimens, suggesting that most of the toxicities were reversible. In this study the major cause of treatment failure was relapse. Although the use of sirolimus was recently suggested to be protective from relapse in lymphoid malignancy,26 further modifications in HCT protocols need to be explored to reduce the relapse risk.
TMA was a major complication in our study that developed in 19% of patients, consistent with an earlier report.12 TMA was significantly associated with Bu/Cy conditioning, which led to the early discontinuation of that regimen from the trial. Increased hepatotoxicity/VOD associated with Bu/Cy in our study is also consistent with a recent report from DFCI showing an increased incidence of VOD in patients conditioned with Bu/Cy in their tacrolimus plus sirolimus GVHD prophylaxis.12 In the ongoing BMT CTN Protocol 0402 (available at https://web.emmes.com/study/bmt2) comparing tacrolimus plus sirolimus versus tacrolimus plus methotrexate for matched related transplants, an increased incidence of VOD in patients conditioned with Bu/Cy in the tacrolimus plus sirolimus arm has led to the early discontinuation of that conditioning regimen.
The higher incidence of TMA/VOD with Bu/Cy is possibly related to the known endothelial toxicity of the conditioning regimen,27,28 coupled with the synergistic effects on canalicular and sinusoidal transport proteins and reduced glutathione–related enzymes from calcineurin inhibitors and sirolimus, leading to reduced protection against oxidative stress and possibly leading to accumulation of toxic metabolites in the hepatocytes.29 We observed higher tacrolimus levels in Bu/Cy compared with Flu/Mel, but not with TBI/VP16 (as shown in Table 3). The tacrolimus levels were not significantly associated with TMA in our univariate analysis; thus, it is unlikely that the increased risk of TMA in Bu/Cy was attributable to the tacrolimus levels. While this analysis showed no threshold effect of the drug levels, the results were difficult to estimate given the limited number of patients and TMA events.
The relationship of GVHD and TMA is difficult to define from this limited experience, although there was a significant association between acute GVHD (grade II to IV) and TMA. Twelve of 16 cases with TMA had acute GVHD, and GVHD anteceded TMA in all cases. This suggests that optimization of tacrolimus and sirolimus dosing may have led to higher drug levels, potentially leading to TMA in addition to ongoing tissue damage from the GVHD itself. Thus, more careful dose adjustment, particularly in the setting of acute GVHD, may reduce the risk of TMA and toxicity profile, although these data do not demonstrate a clear association between the drug levels and TMA, possibly due to the small sample size.
In univariate and multivariate analysis, the most significant factor predicting OS, DFS, relapse, and NRM was disease status. We found no clinical variables significantly predictive for development of grade II to IV acute GVHD within our cohort. Conditioning regimen was not significantly associated with OS or DFS, despite higher incidence of TMA and a trend toward higher incidence of GVHD in Bu/Cy. This may be partly explained by the fact that a majority of patients in this group had good-risk disease. The univariate/multivariate analysis data need to be interpreted with caution, however, because of the heterogeneity of diseases, disease status, and conditioning regimens.
In conclusion, the combination of tacrolimus and sirolimus as GVHD prophylaxis was associated with an excellent NRM rate across multiple conditioning regimens, lending strong support to the ongoing phase III BMT CTN trial 0402. Acute GVHD rates, while higher than those seen by DFCI, were reasonable for the Flu/Mel and TBI/VP16 regimens, with most cases relatively mild and well tolerated. Given the high incidence of associated TMA, tacrolimus/sirolimus prophylaxis must be used with caution in patients conditioned with Bu/Cy and potentially with other regimens likely to cause increased endothelial damage.
Contribution: R.R., R.N., J.M.P., P.P., A.N., and S.J.F. conceived and designed the study; R.R., R.N., P.P., S.S., A.N., D. Snyder, V.P., N.K., E.S., C.K., M.O., A.Y.K., D. Senitzer, and S.J.F. provided study materials or patients; R.R., R.N., J.M.P., P.P., S.S., A.N., D. Snyder, V.P., N.K., J.R., E.S., C.K., M.O., A.Y.K., D. Senitzer, and S.J.F. provided administrative, technical, or logistical support; R.R., R.N., J.M.P., P.P., S.S., A.N., D. Snyder, V.P., N.K., J.R., E.S., C.K., M.O., A.Y.K., D. Senitzer, and S.J.F. collected and assembled the data; R.R., R.N., J.M.P., P.P., S.S., and S.J.F. analyzed and interpreted the data; and R.R., R.N., J.M.P., P.P., S.S., and S.J.F. drafted the article.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Ryotaro Nakamura, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010; e-mail: rnakamura{at}coh.org.
The authors acknowledge the transplant coordinators and transplant nurses for their dedicated care of our patients. We also thank all members of the Hematopoietic Cell Transplant team for their constant support of the program, including the clinical research associates for their protocol management and data collection support. We also thank our scientific writer/editor Dr Sandra Thomas for her critical reading of the manuscript.
This work was supported by the Comprehensive Cancer Center grant (P30 CA 33572), Hem/HCT Program Project grant (PO1 CA 30206-21) and the Tim Nesvig fellowship, which R.N. was recently awarded.
↵* R.R. and R.N. contributed equally to this work.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.
Submitted March 2, 2009.
Accepted October 27, 2009.
© 2010 by The American Society of Hematology
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. Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed. Biol Blood Marrow Transplant 2003;9(10):649-656.
Bensinger WI,
Storer B,
. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001;344(3):175-181.
Alyea EP,
Kim AT,
. Sirolimus, tacrolimus, and low-dose methotrexate as graft-versus-host disease prophylaxis in related and unrelated donor reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2008;14(8):920-926.
Wolff D,
Andree H,
Hilgendorf I,
Casper J,
Freund M,
Junghanss C
. Sirolimus in combination with tacrolimus in allogeneic stem cell transplantation: timing and conditioning regimen may be crucial (letter to the editor). Biol Blood Marrow Transplant 2008;14(8):942-943.
McDonald GB,
Sanders JE,
. Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2004;10(5):320-327.
Armand P,
. Allogeneic transplantation with reduced-intensity conditioning for Hodgkin and non-Hodgkin lymphoma: importance of histology for outcome. Biol Blood Marrow Transplant 2008;14(4):418-425.
DeLeve LD,
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. Role of oxidative stress and glutathione in busulfan toxicity in cultured murine hepatocytes. Pharmacology 2000;60(3):143-154.
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. Cellular target of cyclophosphamide toxicity in the murine liver: role of glutathione and site of metabolic activation. Hepatology 1996;24(4):830-837.
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. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (rapamycin). Pharmacol Toxicol 2001;89(3):133-139.
DOI: https://doi.org/10.1182/blood-2009-03-207563
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Roberto Rodriguez, Ryotaro Nakamura, Joycelynne M. Palmer, Pablo Parker, Sepideh Shayani, Auyaporn Nademanee, David Snyder, Vinod Pullarkat, Neil Kogut, Joseph Rosenthal, Eileen Smith, Chatchada Karanes, Margaret O'Donnell, Amrita Y. Krishnan, David Senitzer, Stephen J. Forman
Blood Feb 2010, 115 (5) 1098-1105; DOI: 10.1182/blood-2009-03-207563
Rodriguez, R., Nakamura, R., Palmer, J. M., Parker, P., Shayani, S., Nademanee, A., Snyder, D., Pullarkat, V., Kogut, N., Rosenthal, J., Smith, E., Karanes, C., O'Donnell, M., Krishnan, A. Y., Senitzer, D., & Forman, S. J. (2010). A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens. Blood, 115(5), 1098-1105. Accessed July 16, 2019. https://doi.org/10.1182/blood-2009-03-207563.
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Сюе́вр () — муніципалітет у Франції, у регіоні Центр-Долина Луари, департамент Луар і Шер. Населення —  осіб (2011).

Муніципалітет розташований на відстані близько 150 км на південний захід від Парижа, 45 км на південний захід від Орлеана, 13 км на північний схід від Блуа.

Демографія

Розподіл населення за віком та статтю (2006):

Економіка

У 2010 році в муніципалітеті числилось 624 оподатковані домогосподарства, у яких проживали 1573,0 особи, медіана доходів виносила  євро на одного особоспоживача

Посилання

 Сайт мерії муніципалітету Сюевр

 Сюевр на сайті французького Національного інституту географії
 Сюевр на сайті французького Національного інституту статистики й економічних досліджень
 [ Розташування муніципалітету Сюевр на мапі Франції та сусідні муніципалітети]

Див. також
 Список муніципалітетів департаменту Луар і Шер

Примітки

Муніципалітети департаменту Луар і Шер

redpajama_set_name: RedPajamaWikipedia


text:
We have been awaiting this announcement for weeks! Disney has just revealed the opening date for the newest BBQ dining option at Walt Disney World. Roundup Rodeo BBQ at Disney's Hollywood Studios is opening on March 23, 2023. "Using some of his favorite toys, games,...
EPCOT International Festival of the Arts Food Menus Announced
by Professor Heather Adamczak | Jan 5, 2023
Every year Disney brings us the EPCOT International Festival of the Arts! This is one of our favorite festivals as it features beautiful art from world renowned Disney artists and their work is displayed and oavwalible for purchase. You can also meet the artist on...
Akershus Royal Banquet Hall Now Opens at 2:45 PM
by Professor Heather Adamczak | Nov 27, 2022
Earlier this month Akershus Royal Banquet Hall opened for character dining once again at Epcot. When they opened up at 4:15 PM and closed at 8:05 PM. Today the hours on the website changed from an opening of 4:15 PM to 2:45 PM. If you're looking to get a dining...
Akershus Royal Banquet Hall Disney Princesses for Storybook Dining Review
Getting dining reservations in the parks has gotten to be pretty cutthroat with the limited options for character meals! Your reservation window opens up and it is a mad dash to see what you can get your hands on. That's why we were thrilled when Akershus Royal...
2022 Disney Parks Holiday Food Guide and More!
by Professor Heather Adamczak | Nov 4, 2022
It sure is beginning to look a lot like Christmas! Today Disney revealed the details behind some of the gorgeous gingerbread displays around the Disney parks and resorts. Not only that, but we got a sneak peek into the treats coming this holiday season as well! So sit...
Whispering Canyon Cafe Holiday Menus Revealed
The holidays are alwasy so much fun at the Walt Disney World Resort. But, where can you find a traditional holiday meal? This year we are very slowly starting to see menus pop up at various locations. The first is Whispering Canyon Cafe at Disney's Wilderness Lodge....
Mickey's Very Merry Christmas Party Foodie Guide 2022
The very first Mickey's Very Merry Christmas Party begins on November 8th! Today, Disney has released to full "Foodie Guide" for the special ticketed event. The Party is held on select nights from November 8 through December 2022, is the ultimate holiday gathering...
Tusker House Restaurant Transitioning to Buffet November 1st
by Professor Heather Adamczak | Oct 18, 2022
Beginning Nov. 1, Tusker House Restaurant will be transitioning back to an all-you-care-to-enjoy, buffet-style dining experience! That means you can go and grab all the food you can handle. What makes this spot nestled in the Harambe Marketplace so special is its menu...
Akershus Royal Banquet Hall Reopening November 4th!
Akershus Royal Banquet Hall will open its doors once again on November 4th, 2022. This character dining experience has been closed since before the pandemic and we have been anxiously awaiting its return! This VERY NEEDED princess dining experience is found at the...
Kona Cafe Reopening November 1st at Polynesian Village Resort
Kona Cafe has been closed for refurbishment at Disney's Polynesian Village Resort for a few months and this week Disney posted an update on its website about the reopening. Here's the announcement: "Kona Cafe at Disney's Polynesian Village Resort is currently...
Disney's Wilderness Lodge Adds New Menu Items!
by Professor Heather Adamczak | Oct 4, 2022
Disney's Wilderness Lodge is getting some delish new upgrades at both Territory Lounge and Roaring Fork. Both of these spots are getting some new additions to their menus, and trust me, they won't disappoint. Today Disney shared a look at these menu items and we have...
2022 EPCOT International Festival of the Holiday's Food Kitchens
by Professor Heather Adamczak | Sep 29, 2022
This year the 2022 EPCOT® International Festival of the Holidays presented by AdventHealth will run from November 25 through December 30, 2022! This week Disney posted the list of the food kitchens coming to the festival this year! You can stroll across 6...
EPCOT Candlelight Processional Celebrity Narrators Announced
Get ready to fill your holiday season with songs at the "Candlelight Processional," returning to the EPCOT International Festival of the Holidays presented by AdventHealth starting Nov. 25. This time-honored tradition has been a part of the holiday season at Walt...
EPCOT 40th Anniversary Foodie List!
This year, October 1 marks the 40th Anniversary of EPCOT. In true Disney fashion, we can't have a celebration without some yummy treats! For select days surrounding the anniversary, various locations will be serving up eats and sips honoring 40 years of fun and...
New Menu Items Coming to Disney Parks
At both Walt Disney World Resort and Disneyland Resort, new drink and menu items have just debuted! Today Disney shared a look at these items and where we can find them. Let's take a look together below: Walt Disney World Resort Starting today, over at Disney's Grand...
New Cocktails Coming to Magic Kingdom Restaurants
Beginning next month some new cocktails are coming to Magic Kingdom restaurants to elevate your dining experience! Over the years Disney has begun to lift its restrictions on where you can drink boozy beverages at the parks. For years you could not find a drop of...

redpajama_set_name: RedPajamaCommonCrawl


Salinas Underground Podcast: SUP #17 9-1-14 with Grab a Beer a Jacket Podcast "Good people drink good beer."
SUP #17 9-1-14 with Grab a Beer a Jacket Podcast "Good people drink good beer."
This is a special episode recorded at Lagunitas Brewery in Petaluma. This a supershow recorded with James and Jonesy from our brother podcast Grab a Beer and Jacket. The folks at Lagunitas graciously opened their doors during their annual Blues concert and we had a great time. A great pork nacho, blues, beer filled time.


text:
Q: randomly replace contents in
* I am trying to make a simple game in JS, where the sum of two random number will be generated, And there is four
 tag which contains also some randomly generated number. The sum result will be placed one of this
 tag. User has to find the right
 and click on it. I am not understanding how to place the sum result in those four
 randomly. Could you please help?

        let number1     = Math.floor(Math.random() * 100)
        let number2     = Math.floor(Math.random() * 100)
        const title     = document.querySelector(".title")
        title.innerHTML = 'What is the sum of '+ number1  + ' and ' + number2 ;

        const num1      = document.querySelector(".nums1");
        num1.innerHTML  = Math.floor(Math.random() * 100)
        const num2      = document.querySelector(".nums2");
        num2.innerHTML  = Math.floor(Math.random() * 100)
        const num3      = document.querySelector(".nums3");
        num3.innerHTML  = Math.floor(Math.random() * 100)
        const num4      = document.querySelector(".nums4");
        num4.innerHTML  = Math.floor(Math.random() * 100)

        let sum = number1 + number2
        console.log(sum)

        // this function i have made to generate random numbers from 1-3,
        //when the number is 1, the 1st li number will contain the sum result
        // when the number is 2, the 2nd li will contain the sume result and so on..

        function randPosition(){
            let randomsPos = Math.floor(Math.random() * 4)+1
        }
        randPosition()

What is the sum of 10 and 4 ?

9

4

6

7

       <button class="btn"> Play Again</button>

A: Using the :nth-child selector will help in this case.
Modify the randPosition function as below
function randPosition(){
    let randomsPos = Math.floor(Math.random() * 4)+1
    const liElement = document.querySelector(`ul :nth-child(${randomsPos})`);
    liElement.innerHTML = sum;
}

The :nth-child selector will select the nth child element of the ul. And the content will be replaced with the sum

redpajama_set_name: RedPajamaStackExchange


He will not be playing. New manager uses GPS and Denton was even worse than McLeod.
Something tells me Denton read this script last year.
2 in 16 league apps not exactly an upgrade is it.
So then, as it reads, he's actually hit the net 16 times this season??? That's a goal scorer. Denton was our top scorer two seasons on the bounce, if memory serves me, he finished as our top goal scorer even after Fullerton refused to play him!!!!!!!!!!!!!!! There are lots of criticisms that can be pointed at him, not by me though, he did a job, his goals got us promoted, he doesn't have any pace whatsoever, but when he gets the right ball in the right area then the chances are he will score.
Now then, I have been slightly critical of Southdale, I have quoted stats that stand as proof that he is not a goal scorer, I would like to bet that if you did the same for Denton his statswould tell a very different story.
Besides which, using the same analogy as above, if Dents signed and then played on Saturday, he would score????
But according to a certain manager Goalscorers do not score goals and If you are not up to GPS you are out.
No, you're wrong! Someone who scores goals isn't a goal scorer.
And don't worry about being in a low league position with the threat of relegation, all you have to do is not look at the league table, BINGO!
Via stats pulled on both of them this season. Since Denton moved to Chesterfield he has played 17 league matches. He has scored 2 league goals.
Since the start of the the season Southwell has scored 6 goals in 30 albeit a poor ratio its still better than Dentons if the pair keep going the way they are now.
There is a reason he keeps getting shunned from this division its not just a bloody coincidence.
He is a conference north player and was our top scorer in that league for which i thank him. As for last season. He was our top goalscorer because Heath REFUSED to drop him. and Fondop whilst not being the answer managed to amass half the amount of goals Denton managed in the last 8 weeks of the season. Nor was it a coincidence that our form picked up once Denton was removed from the team.
Greggs:- I'm bored with it just as much as you!!! I'm sick of people constantly harping on about past players and the possibility of their return. I quite agree, move on. BUT, I get sick of people constantly having a go at the lad. He did a job for us and in the history books his stats will show that he was our top scorer on two consecutive seasons.
The stats I was talking about are career stats, not just this season. And all I'm saying is Southwell's dont stand up as a striker who will get 15 / 20 per season. Which is precisely why I have been constantly repeating myself on these threads saying we need a proven striker or we are in big trouble. I've been saying that since last October!! Quigley is not the answer.
Why would Heath drop a 1 in 3 striker?
The only person your trying to convince on this is yourself, why are his replacements not scoring?
He's not the answer but one things for sure had he played every game for us this season he would have more than the 4 goals from open play that Southwell has.
I'm not trying to convince myself of anything.
The replacements are not scoring because just like under Heath the players are being utilised in the wrong way.
Denton has been effectivly told he isn't good enough for this level twice now.
So why exactly has he only bagged 2 in 17 games for Chesterfield if he's soooo much better than Southwell.
He' s a conference north player simple as that. Emphasised by the fact 14 of his 16 goals have been scored against opposition of that calibre of lower.
You put a 7 foot giant on the goalline at the back post he's bound to score besides that he offered bugger all and was very quickly worked out.
He offers more than Quigley and Southwell I'd have him back tomorrow.
To compare Southwell and Denton's records is ridiculous Southwell has olayed in the Football League with Luton and Wycombe Denton has never been capable of playing at that level.
He must be decent because Chesterfield ha e drawn more than us.
Southwell is a very good player imo. Earlier in the season was crying out to be played centrally with the support of someone like King. Quigley has come in and Dayle has been moved wide right when everyone thought Quigley had been brought in to support him. Dayle scores a very good goal against Solihull (I think) from this position but I want to see him played down the middle with king in behind playing the ball on the deck.
Then you will have to wait until a new manager comes in to have a chance for that to happen.
Thought he did a stint at Huddersfield from Emley/Wakefield.
People have yet again fixated on a player!!! I am not having a go at Southwell, as Ive said before, I like the lad. He runs his socks off working for the team. But he is not a natural goalscorer. Quigley has come in not up to match fitness and has yet to hit the target. My complete argument is that we needed and still do need an out and out goal scorer. There must be a player out there screaming for first team football who cant get in their club team due to the current holder of the shirt scoring for fun??? Offer that player/club a good deal till the end of the season. If we had a scorer we would definitely pull clear of the danger zone..


Quick and easy Omron 3 Series home blood pressure monitor utilizes a simple one touch mode, which can store up to 14 readings at a time while still giving you an accurate reading every time you monitor. Includes cuff that fits both standard and large arms. When you trust your heart to Omron, you?ll be empowered by accuracy.
Convenient product for a patient to use in their home on a temporary basis.
I ordered several for our office and they work very well and the price was cheaper that several other medical website.


text:
The Tragedy Academy
Special Guest: Ryan Cooper - F@#% It. Why Not Me.
Today on The Tragedy Academy, I welcome Ryan Cooper, entrepreneur and author of the book Fuck It: Why Not Me. In this episode, Ryan wears his heart on his sleeve, walks us through the inspiration behind writing his book, and shares his experience growing up with a bipolar mother and later diagnosed with the same mental illness. Ryan's story is one of adversity and anguish yet, through perseverance, he can come out the other side full of gratitude and triumph.
💡 Inspiration for Fuck It: Why Not Me
⚕ Life as a person diagnosed with Bipolar
😩 Managing stress
🧘 Working towards essential things and being mindful
😬 Animosity in the home
Episode Highlights:
[01:03] Ryan was born and raised in Las Vegas, Nevada. He attended Arizona State with honors and a desire to pursue football but recognizing he did not fit the weight requirements, Ryan decided to follow the business side of things. He is now working towards getting his MBA in the sports business.
[02:37] After the passing of his father, Ryan vowed to leave a legacy honoring him. He wrote a book titled Fuck It: Why Not Me and released it on his father's death anniversary. The book is a novel that focuses on Life's hurdles and how he could push forward to become the entrepreneur he is today.
[04:14] Ryan shares the bipolar diagnosis of his mother and himself. He admits to gaining some perspective after being diagnosed, changing his whole outlook on it.
[07:00] Ryan dives deep into his diagnosis and confesses to the uncertainty of his future. Nonetheless, he is determined to be optimistic and recognizes that his diagnosis does not define him, nor will it hinder his Life.
[13:24] Ryan shares his ways of managing stress. He emphasizes the importance of therapy and includes additional activities like exercising and journaling.
[15:08] Ryan expounds on his love and passion for sports, especially now as a coach. He categorizes this as an essential aspect in his Life that provides moments of mindfulness. As a coach, he has the opportunity to help the younger generations get better at a skill while offering advice as both a coach and student.
[18:20] Ryan gives us a peek into his family life. He shares the moment of going from 100-0, having everything in one moment, then having everything taken away from you. While his father was sick, his mother had an accident that landed her in prison, so during this time, the family lost their house, but Ryan was still responsible for taking care of his father.
[27:33] Ryan admits to having no animosity towards his mom. Over the years, they have formed a stronger bond now that they understand their bipolar tendencies. Ryan confesses to resenting her in his late teenage years from fear of having to drop out of school and come back to Las Vegas to take care of her, but that has since dissipated, and now their relationship could not be stronger.
[31:47] Connect with Ryan
Connect with Ryan:
Buy his book: Fuck It: Why Not Me
Instagram | @therwcooper
More episodes from The Tragedy Academy
Susan Gold "Wake Up Little Susie" Trauma through a child's eyes.
Welcome to episode 78 of the Tragedy Academy, where we explore the stories of those who have overcome great struggles and come out on top. This week, Jay sits down with Susan Gold, a woman who has turned her own personal tragedy into a successful career as a producer and talent broker. Susan shares her inspiring journey of using her ability to discern where people are best applied, honed from her own trauma, to make a name for herself in the entertainment industry while offering actionable advice for listeners looking to improve their mental well-being. She shares how life in Montana as a coach now helps her remain at peace. But don't let the heavy topic fool you; this episode is filled with laughter and moments of levity as Susan and Jay bond over their shared love of overcoming adversity. Tune in for a truly uplifting and entertaining conversation on the Tragedy Academy. About Susan: Susan Gold is a talent broker and producer whose career in entertainment has been a testament to her ability to overcome adversity. Growing up in Pennsylvania, Susan faced childhood trauma. She turned to athletics as a way to cope, becoming a nationally ranked Masters Swimmer and finishing third in her age group at the challenging Escape From Alcatraz Triathlon. However, after relocating to New York City and finding success in the cutthroat world of talent representation, Susan struggled with alcoholism. But with the help of therapy and support, she overcame her addiction and used her gifts of discernment and drive to form her own talent brokerage firm, Celebrity Talent. From there, she produced high-profile events and television segments and became a sought-after advisor for brands looking to leverage media placement and celebrity attachment. Join us as we talk to Susan about her journey and how she's used her experiences to help others in the entertainment industry. Key Takeaways: [12:30] Susan shares her story of overcoming trauma and how it led to her success in talent management. [22:00] Susan and Jay discuss the importance of discernment in the entertainment industry and how it can lead to successful partnerships. [30:00] Susan shares a hilarious anecdote about a time she convinced Andy Warhol to do a TV commercial. [42:00] Jay and Susan discuss the importance of resilience in facing rejection and failure in the entertainment industry. [52:00] Susan offers actionable advice on navigating the entertainment industry and making connections that lead to success. "Quotes" "Trauma doesn't define us, but it does shape us." - Susan Gold "Self-compassion is the foundation for healing." - Susan Gold Support Susan! Email: susan@susangoldconsulting.com Website: https://www.susangold.us/ Twitter: Susan Gold (@sgoldconsulting) / Twitter - @sgoldconsulting Instagram: Susan Gold (@susangoldismagical) • Instagram photos and videos - @susangoldismagical Facebook: Susan Gold | Facebook Linkedin: Susan Gold - Executive - SGC, LLC | LinkedIn Support the show! Visit
Anthony Hyland - "Clout"
In this episode of The Tragedy Academy podcast, host Jay Hicks interviews Anthony Hyland, the focus of the new docu-series "Clout." The series details Hyland's personal struggle to clear his name after false allegations of sexual assault were made against him. The episodes provide a raw and emotional examination of the impact of these false accusations on Hyland's life and the lives of those around him, as well as an exploration of the motivations behind the person who made the false allegations. During the interview, Anthony shared some key takeaways from his experience: * False allegations can significantly impact a person's life, and it is essential to understand the history and context surrounding them. * Resilience and determination are crucial when facing difficult challenges. * He is a survivor of sexual assault himself, and the situation was triggering for him. * He emphasizes that it's not just about him; it's about the bigger picture and the message he wants to spread. This conversation is critical today, where false allegations can ruin a person's life and reputation. The docu-series is a must-watch and can be found on YouTube. If you want to learn more about Anthony's story, check out the series and follow him on TikTok under the handle @ispeak1906. Additionally, Anthony also discussed the importance of supporting those who have been falsely accused and the need for a fair and just legal system. He highlighted the role of social media in amplifying false accusations and the impact it can have on an individual's life. He also emphasized the importance of having a support system and how it helped him navigate difficult times. He spoke about the role of his family, friends, and chain of command in supporting him and his journey to clear his name. Furthermore, Anthony also mentioned the impact of the false allegations on his career and life goals. He spoke about his difficulties in continuing his work as a speaker, author, and entrepreneur and how he had to put his life on hold to focus on clearing his name. Overall, Anthony's story is a powerful reminder of the importance of standing up for the truth and the need for a fair legal system. It also highlights the impact of false allegations and the importance of supporting those who have been falsely accused. It's an emotional and thought-provoking interview that will leave a lasting impact on the listeners. Be sure to tune in to the episode and watch the docu-series to hear Anthony's personal story and the lessons he learned throughout his journey. Connect Email: poshmediabiz@gmail.com Instagram: https://www.instagram.com/ispeak1906/ TikTok: https://www.tiktok.com/@ispeak1906 YouTube: https://www.youtube.com/@AnthonyHyland Support the show! * Visit our website to find links to our YouTube channel, other social media, show notes, and more! * Make a beautiful podcast website with Podpage. * Explore professional recording options with Riverside.fm. * Like Jay's t-shirt from this episode? Get your own at
Detention Episode: Professional Fighter Pearl Gonzalez - "The Slappening"
In this special nighttime detention episode of the Tragedy Academy Podcast, host Jay and co-host Gary welcome special guest Pearl Gonzalez, a professional boxer and MMA fighter known for her power in combat sports. Pearl is a rising star in the fighting world, and she's here to talk about her career, aspirations, and life. Oh yeah, and to slap the hell out of Gary for an opportunity to be in Dana White's new PowerSlap league. Key Discussion Points: 🥊 Introducing special guest Pearl Gonzalez, a professional boxer and MMA fighter 🥋 Discussion on Pearl's career, aspirations, and life 👋 Pearl conducts a tryout for the show by slapping Gary, who is the executive producer of the soon-to-be-released reality TV show Powerslap ✊ The importance of representation and setting an example for those in lower socioeconomic backgrounds 🏙 Pearl shares her own humble beginnings, growing up in the Chicago streets with drug-addicted family members 🕊 The power of hope and the impact of family, including the host's grandmother, who is currently battling cancer and using Pearl's fighting spirit as inspiration 🧠 The different forms of expression and the physical and mental toll of combat sports and how it can affect not just the physical body but also the mental and emotional well-being of the fighters 😶 Importance of determination and love for fighting to overcome losses and setbacks in the sport 🏌 The difficulty of getting a good slap right off the bat, comparing it to golfing and the need for proper technique and training Pearl opens up about her humble beginnings, growing up in the rough streets of Chicago with drug-addicted family members. Despite the odds stacked against her, she was able to find her passion for fighting and use it as a way to turn her life around. She talks about the importance of representation and setting an example for those in lower socioeconomic backgrounds and how her story can inspire others to chase their dreams. And how she is driven to remain an inspiration for her nieces and nephews. But the episode isn't all serious talk. Pearl also conducts a tryout for Dana White's new Powerslap League by slapping Gary, the executive producer of the soon-to-be-released reality TV show Powerslap. The moment is ridiculous yet enlightening, as Pearl shows off her powerful slaps, and Gary provides commentary on the technicalities of getting a good slap. The conversation also delves into the difficulty of getting a good slap right off the bat, comparing it to golfing and mentioning that some fighters train on watermelons to get the right technique. They also talk about the mental aspect of training, including using a picture of an opponent to stay focused and motivated. Throughout the episode, Pearl also talks about the different forms of expression and the physical and mental toll of the sport. She discusses the traumatic nature of the sport and how it can affect not just the physical body but also the mental and emotional well-being of the fighters. She also talks about the importance of determination and love for fighting to overcome the losses and setbacks in the sport. The episode ends with a discussion about the power of hope and the impact of family, including the host's grandmother battling cancer and using Pearl's fighting spirit as inspiration. This episode is not only a hilarious and entertaining listen, but it's also an enlightening look at the power of determination, hope, and the impact of representation. It's definitely an episode worth tuning in for. Instagram: ( @pearlgonzalez ) https://www.instagram.com/pearlgonzalez/ Twitter: ( @PearlGonzalez )


Good Food, Great Service, Excellent Coffee! Now with 43 great locations around NZ. So Where Will I Meet You?..... at The Coffee Club.
I was shocked at how much a coffee costs here! Over $5! I think coffee is ridiculously over-priced. Lucky it was a good coffee.


Audiodraft Contest | Create a game theme style (for an explainer vi..
We are looking for a funny theme song with some tension. With early 90s adventure games style. (Monkey Island, Day of the Tentacle, etc...). Could range from the "dub style" of Monkey Island to something more "orchestral" like in Day of the Tentacle.


text:
Netscape Browser je webový prohlížeč pro operační systém Windows vydávaný společností AOL, ale vyvíjený společností Mercurial Communications. Jedná se o pokračovatele řady prohlížečů Netscape. Na rozdíl od Netscape 6 a 7, které byly založeny na balíku Mozilla Suite, je Netscape Browser založen na Firefoxu obdobně, jako třeba webový prohlížeč Flock. Jako řada dalších produktů od AOL podporuje AOL Instant Messenger. Prohlížeč je též zajímavý svou schopností přepínat se mezi renderovacím jádrem Gecko, které používají prohlížeče postavené na Mozille a jádrem Trident, který používá prohlížeč Windows Internet Explorer. Dne 28. prosince 2007 Netscape oznámil, že z důvodů nezájmu uživatelů o novou verzi končí s dalším vývojem webových prohlížeče Netscape.

Přehled verzí
Netscape Browser se poprvé objevil na trhu 30. listopadu 2004 jako veřejný "prototyp".

Související články
 Mozilla Firefox
 Netscape
 Netscape Navigator 9

Reference

Externí odkazy
 Domovská stránka Netscape Browser

Mozilla
Netscape
Webové prohlížeče


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Q: Border effect to LinearLayout I would like to get linearlayout border effect like the image below:

Is this possible? I don't wanna use one layout inside another layout. If so how do I do it?
I tried the following:

<corners android:radius="4dp" />

<stroke
    android:width="4dp"
    android:color="@color/layoutcolor_net" />

<gradient
    android:endColor="#BDBDBD"
    android:gradientRadius="250"
    android:startColor="#E0E0E0"
    android:type="radial" />

<padding
    android:bottom="30dp"
    android:left="30dp"
    android:right="30dp"
    android:top="30dp" />

I apply the gradient properly but my text is not shown.
I am applying this to relativeLayout:
                <RelativeLayout
                android:id="@+id/receivedLayout"
                android:layout_width="match_parent"
                android:layout_height="0dp"
                android:layout_weight=".33"
                android:background="@drawable/gradientShow"
                android:gravity="center" >

                <ImageView
                    android:id="@+id/receivedImage"
                    android:layout_width="wrap_content"
                    android:layout_height="wrap_content"
                    android:layout_centerHorizontal="true"
                    android:background="@drawable/recieved"
                    android:paddingTop="5dp" />

                <TextView
                    android:id="@+id/receivedText"
                    android:layout_width="match_parent"
                    android:layout_height="wrap_content"
                    android:layout_below="@+id/receivedImage"
                    android:gravity="center"
                    android:paddingTop="5dp"
                    android:text="@string/transaction_received"
                    android:textSize="14sp" />
            </RelativeLayout>

Thanks!

A: you should checkout the 'shape drawables' section of the reference guide.
http://developer.android.com/guide/topics/resources/drawable-resource.html#Shape
There are lots of things you can do with shapes. For example:
<shape
android:shape="rectangle">
<gradient
    android:startColor="#FFFF0000"
    android:endColor="#80FF00FF"
    android:angle="45"/>
<padding android:left="7dp"
    android:top="7dp"
    android:right="7dp"
    android:bottom="7dp" />
<corners android:radius="8dp" />

save that file as res/drawables/gradient.xml folder and refer to it like this in a textview or some other view:
<TextView
android:background="@drawable/gradient"
android:layout_height="wrap_content"
android:layout_width="wrap_content" />


text: Q: Make the usepackage sanitize-umlaut work The index list at the end as a register of all \index{...} is sorted alphabetically. However, non-standard characters like German umlauts are by default treated as symbols and, therefore, placed at the beginning. As a workaround, I found the usepackage sanitize-umlaut. But still this does not really work as it indeed sorts the terms correctly, but erases the umlauts. (Yes, I also use the \usepackage[ngerman]{babel}.) How do I get the index list to work properly?


A story from "The Frumpy House"
as most of my followers/readers out there know, I have an etsy shop...a shop for vintage items. If you didn't know, check out the righthand sidebar on my blog that links to the shop and has pics of newly listed items.
A few weeks ago, Greg and I, made an impromptu day trip to Detroit. We had never been there together. I hadn't been there since I was a kid.
My mom's sister, Joyce has lived and worked in Detroit for the last 35 yrs or so. She has been at a mission in the downtown area. Well, the mission has of course people giving them things (some people leave them their whole home & contents) to do with as they want. Usually, they sell the homes and items to help fund the mission. One of the things my aunt does throughout the summer is run yard sales. Just down the block from the mission they have a large (I mean LARGE) garage/storage facility that is just piled high with items that they set out, hang up or pile up for people to look at and buy.
So of course, we made the trip!
I wish I had taken pics of the place. It was amazing. Like going to the largest rummage sale ever!! Rummage I did....for hours, to my hearts content. I found some pretty amazing and fun things. I was digging through huge bags of clothes, as in moving these bags out of the way to get to some boxes, to get to boxed items that I hoped would hold some treasures.
Treasures found!! So, here are some pics that show a few of the things I have listed. There are more to come!!
The biggest Granny Square afghan EVER!!
Mattel toy gun, not listed yet, have to research!
The 100% Wool Beret, not the cutie, is for sale!
Melamine Fish shaped Hors d'oeuvre Set!
There is soooo much more, I'm hoping to head back to the Motor City and find some more goodies, possibly @ the end of the summer!! We'd like to take the girls to the Detroit Zoo....Maybe a dual purpose trip!
***So, I'm thinking of marking items that are from the mission in the shop. Would it make any difference to any of you readers in making a purchase if you knew a certain percentage was going to a good cause? Let me know what you think, I may or may not, depending on feedback!
As of today we will no longer wake in the night as we hear the rain pitter patter on the skylight! We will no longer jump up and rush the towels & buckets to catch the aforementioned rain as it ran in rivulets down the aforementioned skylight.
THAT my friends is a good thing...& I am very happy!!
My dad, the best "free" contractor around....sometimes whatever is freshly baked is enough for payment....worked hard all day to repair the roof & close up the skylight.
I'm usually the apprentice I just don't get to do all the technical stuff, I'm more of a hander-upper.
Thanks again dad! It's gonna be my job to "finish" the job....cleaning all the dust & debris up tomorrow!
PS: since I had an appointment in our nearest "large" town (re: has a Wal-Mart & more than one fast food restaurant) I did a little thrifting.....will share some fun things soon!
She is the worst of times!! Yes, my lovely Lauryn! My first born, my golden haired beauty, my strong willed eldest!!
She can go for days at a time being petulant, moody, oppositional & grotesquely whiney!! Yet the girl has all the lights on, plus a few amped up flashlights if you know what I mean!!
She has brains in her belfry. Illustrious gray matter in her noggin. She's got them there smarts y'all!!!
Lauryn is blessed with many things....she is quite stunning with her blue almond shaped eyes, symmetrical facial features, naturally curly blonde hair.....she has an outgoing personality, odd little sense of humor & smarts from somewhere other than maternal or paternal!!
Golly, that girly is S.M.A.R.T.
We are blessed enough to send her to a private Christian school which not only teaches her her ABC's and 123's, but the beliefs that we hold dear!!
The end of the year is much like any other school! She got her last report card, a printout of how she scored on the National CAT testing and of course the bill!! Everything looked great, well it had been great all year! She'd been on A Honor roll each quarter (95% avg or above in each subject) so nothing new to us!
Then comes Honors Banquet, where all students are recognized for their achievements throughout the year! Yeah Tigers!!!
We were sitting toward the back of the auditorium, due to the nonstop action of the 5 yr old girly!! But we weren't missing a thing!
Imagine with me now.....name, blah, blah, blah, applause.....no disrespect to anyone, it's just fewer words when you "blah" a bunch out!!
Outstanding work by all! Lauryn's name was called & she was given her certificates for music (did you see the penny whistle post?), volleyball (she actually got to play a game this year due to kids being sick & the other school having a young team too), and pins for recognition in each subject that she had the highest % (or GPA).
Ummm, HELLO! 5 PINS!! Heck yeah!! That's my girl!!!
Math, social studies, science, English, and spelling!! Whoooeee!
She had so many things to hang onto, she started dropping them!
Then comes the fun part....trophy time!!
Posing for me....she looked upset about the wait didn't she!?!?
Okay, that's all the excitement a momma can take! I was about to burst my buttons, and NO it was not from the fine dinner we had beforehand!
So the night progresses & many other wonderful students get awards....then some more come Lauryn's way!
Our retired principle still comes to the school everyday & works with the students who may need a little extra help. She is very involved in the group 'Daughters of the American Revolution'. Embarrassing as it is I'm not sure what all this group does, but they are national. Each fall the children are given a topic to write an essay on & draw a stamp. This years topic was "keeping history alive"....I think! Eeep!! Bad mommy....anywhoo, Lauryn won 1st in her grade level for district, state & honorable mention @ national level. I'm pretty impressed & she was given a $10 prize, she was VERY impressed!
The last major award of the night goes to the students who have memorized 8 months of scripture (a passage of about 12-20 verses)! Lauryn received a trophy for that accomplishment too!!
Whew, this has been a lengthy post. I usually try to keep my insanity to a low level...but for reals, this stuff is too good to not share!!
SO CONGRATS LAURYN, you've gone and doned us parental units proud!!!!
Oh, did I fail to mention Lauryn is 7 and just completed the 3rd grade?!? No? Well, I tried to tell ya the girly is S.M.A.R.T.....she's also a smarty pants (so don't hate, I'll be the first to tell you none of us is perfect)!!
I Love my Lauryn & I'm really excited to see where her smarts will take her in life!!


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Tour to Watch Out for: The Secret Valentine Tour with We The Kings, The Maine, The Cab, There For Tomorrow, and VersaEmerge
Leave a Comment	/ Reviews / By Lauren / January 6, 2009 March 18, 2021
By: Lauren Campbell
The tour starts February 6th in Richmond,VA and will come to the area on 2/8 at the Chance Complex in Poughkeepsie, NY before ending in Millvale, PA on March 4th. If being headlined by We the Kings and perennial "The Hills" band The Maine aren't a big enough draw alone, this tour features two of my new favorite bands of the moment and that should definitely be on your watch list for the next big thing.
The Cab is a pop punk- rock band hailing from Las Vegas. Their first album, Whisper War, was released this past April and have been called "The Band You Need To Know 2008" by Alternative Press. There first single was the insanely catchy "One of those Nights" written by Patrick Stump of Fall Out Boy and features vocals by Brendan Urie of Panic at the Disco and Stump, which is quite fitting since this song and many others off the record sound like the melding of these two fellow label mates with a little 'NSYNC era JT mixed in. By now I am sure you have heard their third single, the albums stand out track, which has been hitting the airwaves – the infectious and soulful pop song "Bounce". It's an unapologetic pop song which is reminiscent of boy bands yet has a rock edge. The album also highlights pop-punk anthems like "High Hopes in Velvet" and "Take My Hand" which will have you continuously rocking out while "Risky Business" will do exactly as the lyrics say and have you "stop asking, keep dancing." This is one CD that I actually enjoyed every track with its collection of upbeat songs that are extremely likeable and are sure to be stuck in your head after a few listens. The combination of vocal talent, thoughtful lyrics and impressive melody will leave the listener mesmerized by this new band's talent all the way 'til the last note.
Watch The Cab's video "The Bounce" below and check out their music on
The Cab – Bounce
There For Tomorrow is an extremely talented and cute Florida alternative rock/ emo band. I first saw this band a few month ago when they were opening for Anberlin and Scary Kids Scaring Kids. I have to say I was blown away by their performance. I had never heard of this band before but after their amazing, high energy set I was a fan. Aside from their stylish matching suits and perfectly groomed hair, you were held captivated with their strong stage presence and quality songs. Their self-titled 7 song EP is definitely worth giving a listen. Their sound is far more mature than the crop of pop-punk copycats out there but they consistently exhibit an indelible ear for true pop appeal in their tunes. Their adrenaline filled album opens with swirling guitars, heavy riffs, and vocals which switch between kindness and assertiveness like the opening tracks of "Deadlines" and "Pages" (the bands breakout song). Their other songs also embrace big, epic choruses and chunky guitars, like the melodic sing-along "Remember When (Used to Be Used to It)", the beautiful "Waiting" with its Piano driven bridge, the biting track "Addiction and Her Name", and the swirling guitars of their extremely catchy lead single "No More Room To Breathe". The EP finally closes with the terrific "Taking Chances" a hard-edged progressive rock track with mincing melodies. Overall their songs are well crafted with lyrics that are both reflective and relateable with hooks that are extremely catchy. If you like Anberlin or Red Jumpsuit Apparatus, definitely check out this band. LIsten to them now on


text:
Nassim Assefi
global health physician~writer~curator~thrillionaire
Nassim's 1st Novel, Aria
Aria was published by Harcourt in 2007 and 5 Foreign Presses (in Dutch, Persian, Portuguese, Slovene, and Taiwanese). It is currently out of print, but available digitally, on Amazon, and in libraries. Audiobook is available via Audible and ITunes.
Click here for a reader's guide with discussion questions and answers.
Click here for references related to themes in Aria (grief, death of a child and spouse, dwarfs, epistolary prose, mother-daughter relations, Tibet, Iran).
Reviews of Aria
From Jenna Blum, author of Those Who Save Us: "With elegance and grace, Ms. Assefi maps her bereaved heroine's flight through numerous countries and into the uncharted territory of grief. Sometimes raw, sometimes clinically detached, Aria is always human, and in the end, it soars."
From Rory Stewart, author of The Places In Between and The Prince of the Marshes: "A haunting book, painfully open in its emotions, enacting in lyrical prose, an Iranian-American's loss, atonement and reconciliation with Iran and powerfully revealing of the discordancies and echoes that define the interaction between American and Persian culture."
From Rebecca Brown, author of ten books including The Gifts of the Body, The Last Time I Saw You, and Excerpts from a Family Medical Dictionary: "How long does grief last? How far away can we run to try to get away from it? What happens if it stays with us forever? In this wise and compassionate debut novel, Nassim Assefi looks at questions of memory, love and grief as she takes us to Tibet, China, Guatemela, her homeland Iran and, most importantly, the human heart."
Review from John Marshall, book critic of the Seattle Post Intelligencer: Aria "beguiles with its honesty, humanity, empathy and insight... a small gem of a debut novel that manages to address huge issues in an affecting manner, from the immigrant experience in America to the aftershocks of tragedy to the search for family heritage and spiritual comfort." Read the entire review.
Review from Bharti Kirchner of the Seattle Times: "It is the charm, intelligence and dignity of Assefi's writing that make this a worthwhile read."
Review from Lindsey Rowe of Seattle Magazine: "Assefi's writing is packed with potent emotion and poetic sentences...Aria is an excellent first novel and a worthy treatise on grief."
Review from Bob Willliams of the Compulsive Reader Book Blog: "There is much of talent in this remarkable book. It is a serious meditation on the greatest misfortune in life and an interesting display of the growth of the persons involved. It gains a certain topicality in the abundance of material from a part of the world little known or understood. Thus Aria stands out as notable achievement and should appeal to many discriminating readers."
From the Rabbi Michael Goldberg, PhD, hospice chaplain, university professor, author: "Aria is without doubt one of the most realistic accounts of grieving I have read, and certainly, the most exquisitely literate."
Nassim has chapters in these 3 books, too
(click on each of those blue words in the above sentence to be directed to more information)
Connect with Nassim on Social Media ------->


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Magnolia Acquires BEST MAN DOWN
By The Critic | February 7, 2013
The Wagner/Cuban Company's Magnolia Pictures announced today that they've acquired North American rights to BEST MAN DOWN, a warmly funny new comedy from writer/director Ted Koland, starring Justin Long, Jess Weixler, Tyler Labine, Addison Timlin and Frances O'Connor. The film was produced by David Abbitt, Jen Roskind and Sharyn Steele.
When their obnoxious and over-served best man, Lumpy (Labine) unexpectedly dies at their destination wedding in Phoenix, bride and groom Kristin (Weixler) and Scott (Long) are forced to cancel their honeymoon and fly home to the snowy Midwest to arrange for his funeral. But when they arrive they realize that there was a lot more to their friend than met the eye.
"We are pleased to be handling BEST MAN DOWN, a charming film that features excellent performances from a completely winning cast," said Magnolia President Eamonn Bowles.
"It's incredibly exciting to partner with Magnolia on my first film, a company that's made a brand for itself by bringing unique, compelling stories to the screen," said writer/director Ted Koland
Magnolia plans a summer release through their Ultra VOD program, debuting the film on all VOD platforms a month prior to its theatrical release.
Category: Movies Tags: Addison Timlin, BEST MAN DOWN, Frances O'Connor, Jess Weixler, Justin Long, Tyler Labine


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English History Makes Riveting Drama
Gerard Raymond | February 3, 2015
The story of Henry VIII, the English king who rid himself of several inconvenient wives and instituted the Church of England in the process, is a familiar tale. But Wolf Hall: Parts 1 & 2, the new Broadway epic drama that takes you behind the scenes of Henry's Tudor court, delivers a fresh and exciting take on this well-known piece of history.
The two-part Royal Shakespeare Company production, adapted from Hilary Mantel's prize-winning best-selling novels, Wolf Hall and Bring Up the Bodies, commences performances at Broadway's Winter Garden Theatre on March 20. It covers the nine years of King Henry's turbulent reign, during which the lusty monarch annulled his marriage to Catherine of Aragon so he could marry Anne Boleyn, who he then had executed so he could marry his third wife, Jane Seymour.
King Henry's marriages (he eventually had six wives) and his efforts to secure a male heir have long been popular fodder for stage, film, and television drama — most recently the steamy, bodice-ripping Showtime TV series The Tudors. "What people don't know is the story of Thomas Cromwell," says Jeremy Herrin, director of Wolf Hall: Parts 1 & 2, which arrives in New York following two sold-out engagements in England at the RSC home in Stratford-Upon-Avon and in London's West End. "Cromwell was at the heart of all the intrigue, the guy who kept the country moving forward, and his story is a fascinating one."
"In Hilary's books, you get a real look under the skin of those characters, and so you have a really complicated and nuanced version of these people who are all trying to survive in a very hostile world," Herrin continues. "And that's what we tried to take on to the stage — getting the audience to understand them afresh. It's like House of Cards, The Godfather, The Sopranos: It has got all of that intrigue and all of that decision-making in smoky rooms. Games are being played here for the highest stakes."
Mantel's Tudor period novels (the first two in a projected trilogy) are told from the perspective of Cromwell, a blacksmith's son whose rise to the position of the king's indispensable courtier and statesman was quite unprecedented. Wolf Hall skews the usual portrait of Cromwell, who in previous versions of this story — most notably Robert Bolt's A Man for All Seasons — is presented as a personification of evil, the villain who brings down the sainted Sir Thomas More because of his opposition to the king's second marriage.
Cromwell (portrayed in Wolf Hall: Parts 1 & 2 by English actor Ben Miles) comes across as a "keenly modern character," observes Herrin. "Even in that particular world, the way he thinks feels very contemporary," the director explains. "He is connecting problems and finding solutions and leading ordinary people along whilst pursuing a whole range of religious objectives, whilst also looking after his family, whilst creating a network of his sympathizers — all without getting so much power that he overtakes his boss."
"Audiences just love an antihero," Herrin continues. "There is something about our culture or our time in history that we love characters who are morally complicated. Cromwell's morality is wonderfully opaque and you can discuss long into the night his motivations and the real meaning behind his actions, and yet you are always interested in everything that he does." The man himself was executed at the peak of his power in 1540, a mere four years after second part of Wolf Hall concludes; his last years will be the subject of The Mirror and the Light, the concluding part of the Tudor trilogy that Mantel is currently writing. It seems now, five centuries after the actual events took place, that Thomas Cromwell and not Thomas Moore is the man for all seasons.
Wolf Hall: Parts 1 & 2 (adapted by playwright Mike Poulton) deftly condenses Mantel's two weighty tomes, which run into more than 1,000 pages in print, into just over five and a half hours on stage. "A lot of the scenes were translatable straight from the novels, but it's a different experience," says Herrin. "People were really surprised at how funny it is because they were expecting something worthy and historical," he reports. "The audience is sort of taken aback at how contemporary the language is, how fresh the concerns are, how understandable the history. That is a tribute to both Mike and Hilary."
Coincidentally, starting just in January, the British Broadcasting Corporation began airing a six-part television series based on the same two novels, which Herrin expects will have a different approach to the texts. "We had to embrace the medium of the stage so there is no apology that our production is a theatrical event on a large scale." (The two parts, playing in repertory, can be seen as a marathon event with a dinner break in between or as two separate evenings.) "You are going to get two big theatrical events," the director promises. "It is thrilling and wide-ranging, with loads of momentum and fun; you don't get that kind of quiet intimacy that you can get from reading the novel."
"Where possible, we have used dance, lighting, change of focus, and theatrical surprise in order to deliver some of the key events that would otherwise take a minute or more to do in terms of dialogue," continues Herrin, who describes his production as "realistically costumed in a theatrical environment." The period costumes and abstract sets are by Christopher Oram (Tony Award winner for Red) and lighting is by Paule Constable (Tony Award winner for War Horse). "The story-telling is fast and it is furious," he adds. "The watch word of the production is not to waste the audience's time, so we segue from one space to another with great élan and trip through history really quickly. Every now and then there is a spectacle, a bit of pageantry, there are political scenes, street scenes, family scenes, and court scenes, and it all adds up to a rather heady and entertaining mix."
A Christmas Story and Rent to Receive Live TV Productions
Sneak Peek: Sunday in the Park with George
Tony Winner Idina Menzel Set for Off-Broadway Premiere of Skintight


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Home :: Tartan Times :: College celebrates 2016 graduates
College celebrates 2016 graduates
Nearly 140 students were recognized this year in the MacMurray College Class of 2016. The Baccalaureate and 165th Commencement ceremony was held May 7, 2016.
The keynote speaker was Sister Rosemary Connelly, a member of the Religious Sisters of Mercy, who is the executive director of Misericordia Heart of Mercy in Chicago. MacMurray also awarded an honorary Doctor of Public Service to Francis Kateh, a 1991 graduate of MacMurray and the deputy minister for Health Services, chief medical officer for his native Republic of Liberia.
See the entire Class of 2016.
See photo galleries of Commencement.
There will be more photographs next week of the Commencement weekend ceremonies, events and celebrations.
John Honnen, New Media Coordinator
Work: 217-479-7181 | Cell: 217-491-2110


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Fort Hood gunman to appear in court
An Army psychiatrist who killed 13 people in a shooting rampage is set to appear in court
Fort Hood gunman to appear in court An Army psychiatrist who killed 13 people in a shooting rampage is set to appear in court Check out this story on detroitnews.com: http://detne.ws/1CCMENM
AP Published 10:18 a.m. ET Jan. 29, 2015
Former Army psychiatrist Maj. Nidal Hasan(Photo: AP)
Fort Leavenworth, Kansas — An Army psychiatrist who killed 13 people in a shooting rampage at a Texas Army base is set to appear in court.
Nidal Hasan is scheduled to attend a hearing Thursday at Fort Leavenworth, Kansas, where he is being held on military death row. Army officials say the judge, Col. Tara Osborn, wants to review "routine matters" in Hasan's case.
Among those issues is who defends Hasan during his appeals. His lead defense counsel is now an Army judge but has continued to represent him.
Officials at Fort Hood have yet to review Hasan's case nearly 18 months after he was sentenced to death.
That review is one of several mandatory steps in military death penalty cases.
Read or Share this story: http://detne.ws/1CCMENM


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