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Author Affiliations
- Gareth J. Morgan1⇓,
- Faith E. Davies1,
- Walter M. Gregory2,
- Sue E. Bell2,
- Alexander J. Szubert2,
- Nuria Navarro Coy2,
- Gordon Cook3,
- Sylvia Feyler4,
- Peter R.E. Johnson5,
- Claudius Rudin6,
- Mark T. Drayson7,
- Roger G. Owen3,
- Fiona M. Ross8,
- Nigel H. Russell9,
- Graham H. Jackson10 and
- J. Anthony Child2
- for the National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group
- 1The Institute of Cancer Research, Royal Marsden Hospital, London
- 2University of Leeds, Leeds
- 3St James' University Hospital, Leeds
- 4Calderdale and Huddersfield NHS Trust, Huddersfield
- 5Department of Haematology, Western General Hospital, Edinburgh
- 6Royal Devon and Exeter Hospital, Exeter
- 7University of Birmingham, Birmingham
- 8Wessex Regional Genetics Laboratory, The University of Southampton, Salisbury
- 9Department of Academic Haematology, The University of Nottingham
- 10University of Newcastle, Newcastle-upon-Tyne, UK
- Correspondence: Gareth J. Morgan, MD, Section of Haemato-Oncology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Surrey SM2 5NG, UK. Phone: international +44.2087224265., Fax: international +44.2087224432., E-mail: gareth.morgan{at}icr.ac.uk
Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation.
Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma.
Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias.
Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111)
High-dose therapy (HDT) combined with autologous stem-cell transplantation (ASCT) provides superior response and survival outcomes versus standard chemotherapy in patients with newly diagnosed (ND) multiple myeloma (MM).1,2 Standard induction chemotherapy regimens, however, are often associated with hematologic stem-cell toxicity, which may compromise the collection of stem cells for ASCT. Thalidomide is active in MM3–7 and produces little hematologic toxicity, indicating that it may be preferred for use as induction therapy.8 Previous studies evaluating thalidomide, as a component of induction therapy, have shown that it improves response rates3,4,6,9–12 and progression-free survival (PFS),4,6,10,12,13 and provides similar10,12,13 or improved6 overall survival (OS) rates versus non-thalidomide-containing regimens. Thalidomide also appears to be well tolerated in this setting and is associated with an acceptable rate of adverse events.6,9 The demonstrated efficacy, lack of myelosuppression, and overall tolerability of thalidomide provide a strong rationale for its incorporation in standard induction regimens for patients presenting with NDMM who may be eligible for ASCT. Combination vincristine, doxorubicin, and dexamethasone (VAD) is considered a standard infusional induction therapy for younger MM patients prior to HDT and ASCT.14,15 It has previously been shown that the addition of cyclophosphamide to VAMP (vincristine, doxorubicin, and methylprednisone), a regimen very similar to VAD, increases response rates.2,16 Having developed an oral induction regimen comprising cyclophosphamide, thalidomide, and dexamethasone (CTD),17,18 we compared its efficacy and safety to that of cyclophosphamide plus VAD (CVAD) in a large randomized trial setting whereby, apart from the difference in the mode of administration, thalidomide was in effect an alternative to vincristine plus doxorubicin.
Design and Methods
The MRC Myeloma IX trial was a multicenter, randomized phase III trial. The protocol was approved by the relevant institutional review boards and ethics committees. All patients gave written informed consent.
Eligible patients were aged 18 years or more and had symptomatic MM. Exclusion criteria were pregnancy, asymptomatic myeloma, solitary bone plasmacytoma or extramedullary plasmacytoma, previous or concurrent active malignancies, and acute renal failure (defined by a serum creatinine level of >500 μmol/L, unresponsive to 72 h of rehydration, urine output <400 mL/day, or need for dialysis).
Samples for fluorescence in situ hybridization (FISH) analysis were collected at study entry to determine the cytogenetic makeup of the patients. As the number of patients in each subgroup was too small to analyze individually, patients were classified as having either a 'favorable' or 'adverse' interphase FISH. Adverse interphase FISH was defined as t(4;14), t(14;20), t(14;16), gain(1q), del(1p32), and del(17p). Favorable interphase FISH was defined as the absence of any of these abnormalities and included hyperdiploidy, t(11;14), and t(6;14).
Patients were assigned to either an intensive or non-intensive treatment pathway19 based on performance status, clinician judgment, and patient preference. In the HDT pathway, presented here, patients were randomized to 21-day cycles of CTD (oral cyclophosphamide 500 mg/week, oral thalidomide 100 mg/day increasing to 200 mg/day if tolerated, and oral dexamethasone 40 mg/day on days 1–4 and 12–15) or CVAD (oral cyclophosphamide 500 mg/week, vincristine 0.4 mg/day, doxorubicin 9 mg/m2/day as a continuous intravenous infusion for 4 days, and oral dexamethasone 40 mg/day on days 1–4 and 12–15), given for up to 6 cycles until maximum response, after which patients in both groups received high-dose melphalan (200 mg/m2) and ASCT (CONSORT flowchart; Figure 1). Randomization was on a 1:1 basis and open-labeled, using minimization based on treatment center, hemoglobin (males: <11.5 g/dL vs. ≥11.5 g/dL; females: <9.5 g/dL vs. ≥9.5 g/dL), serum calcium (<2.6 mmol/L vs. ≥2.6 mmol/L), serum creatinine (<140 μmol/L vs. ≥140 μmol/L), and platelet levels (<150×109/L vs. ≥150×109/L). All patients were randomized at study entry to receive sodium clodronate (1600 mg/day) or zoledronic acid (4 mg every 21–28 days) until progression.
Cyclophosphamide and granulocyte colony-stimulating factor were recommended as priming therapy prior to stem-cell collection, and it was assumed that the impact of mobilization was the same in both arms. Venous thromboembolism (VTE) prophylaxis was given at the discretion of the individual clinician and was not otherwise specified in the protocol. The advice given suggested that low-risk patients should receive aspirin prophylaxis and high-risk patients should receive warfarin or a low molecular weight heparin. Risk status was defined according to Palumbo et al.20
Outcome measures
During the running of this protocol, the criteria for assessing response to treatment were updated from the European Group for Bone and Marrow Transplantation (EBMT) criteria to the International Myeloma Working Group uniform response criteria.21,22 To reflect this, a modification of the International uniform response criteria was used retrospectively to assess response in this manuscript. The modification included the use of the minimal response (MR) category defined as 25–49% reduction in serum M-protein level and 50–89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h.21 Complete response was defined as negative serum/urine immunofixation, no soft tissue plasmacytomas, and less than 5% plasma cells in the bone marrow. Immunofixation-negative cases without available bone marrow samples were reported as very good partial response. Overall response rate was defined as achieving at least a partial response (PR). Response was assessed after induction and 100 days after ASCT. All assessments were reviewed centrally.
PFS was defined as the time from initial randomization to documented progression or death. Patients with missing follow-up data or those not known to have progressed or to have died at the time of analysis were censored at the last date they were known to be alive and progression-free. OS was calculated similarly as the time from initial randomization to the date of death. VTE and acute renal failure were required to be reported for all patients if they occurred during the study period, or until death or disease progression.
Statistical analysis
The trial was designed to demonstrate that CTD was non-inferior to CVAD with a calculated sample size of 1,080 patients, based on an assumed 40% 5-year OS for CVAD, a non-inferiority margin of 7% (i.e. 33% OS for CTD; hazard ratio [HR], 1.2), a one-sided modified log rank test, at 5% significance and 80% power. If 366 patients were entered, the trial would be powered to detect an increase in the number achieving a CR 100 days after ASCT from 50 to 65% (80% power at 5% significance). The planned number would provide more than 80% power.
For the per-protocol population analysis, patients were analyzed according to the treatment they received. As the intent-to-treat was likely to be less conservative when testing non-inferiority, the per-protocol analysis is presented for the results overall and the intent-to-treat population is used for response assessment after induction and the subgroup analyses. The analysis of response post-HDT was based on the population that received HDT followed by ASCT. In patients who did not receive HDT, response was not assessed at a time that would be directly comparable to 100 days after ASCT.
The assumption of no interaction (chemotherapy effect depending on bisphosphonate and vice versa) between induction chemotherapy and bisphosphonates was prospectively tested before end point assessment in Cox's regression models not adjusting for the minimization factors. Primary end points were response, PFS, and OS, with quality of life (to be reported separately) and toxicity as secondary end points. For PFS and OS, Cox's proportional hazards models were used to compare chemotherapy treatment groups while adjusting for bisphosphonate treatment group and the minimization factors. Proportional hazards were assessed by plotting the hazards over time for each arm, and were found to hold. For response, groups were compared with respect to the proportion achieving PR, VGPR, or CR using logistic regression to account for bisphosphonate and the minimization factors (excluding center post hoc because numbers of patients were low at some centers). Post hoc analyses used Fisher's exact test. Statistical analysis was performed using the SAS 9.0 (SAS Institute Inc., Cary, NC, USA) or Fortran software. All hypothesis tests and CIs are two-sided and at the 5% significance level. The primary end points were ranked and no claims on a rank lower than or equal to the first whose hypothesis could not be rejected were made; in this, PFS and OS have equal ranking, and response a lower ranking.
The trial commenced in 2003 and terminated in 2007, recruiting 1,970 patients from 121 centers. A total of 1,114 patients were assigned to intensive therapy with 1,111 evaluable (Figure 1); 556 were randomized to CVAD and 555 to CTD. However, 540 patients actually received CVAD and 553 received CTD (including 5 patients initially randomized to CVAD), and these patients formed the per-protocol population (n=1,093). The median follow up for patients in this study was 47 months (range 0–74 months). On January 20, 2009, the Trial Steering Committee agreed to unblind the chemotherapy results. Here, a cut-off date of October 5, 2009, is used. Patients' characteristics at baseline were well balanced between the two treatment groups (Table 1). The median patient age was 59 years (range 31–78 years). Overall, 62% of patients were male, 25% had stage I disease, 34% had stage II disease, and 31% had stage III disease according to the International Staging System. The median β2-microglobulin level was 4.0 mg/L (range 0.1–114.1 mg/L). A small proportion of patients aged over 70 years (n=17, 1.5%) were included in the study; 9 patients were randomized to receive CTD induction and 8 to CVAD. Of these 17 patients, only 3 patients (2 CTD and 1 CVAD) subsequently received HDT.
A total of 749 patients (67.4%) received HDT followed by ASCT. The median age of patients who received HDT was 58 years (range 31–72 years) and the median age for those who did not receive HDT was 61 years (range 31–78 years).
The overall response rate for the intent-to-treat population after induction therapy was significantly higher with CTD than CVAD (82.5% vs. 71.2%; P<0.0001) (analysis performed on the intent-to-treat population, Table 2). The post-induction CR rate was 13.0% in patients assigned to CTD and 8.1% in patients assigned to CVAD (P=0.0083). Response rates at day 100 in patients who received HDT with ASCT were similar in both treatment groups (91.6% CTD vs. 90.0% CVAD; P=0.45), but the CR rates were statistically significantly higher in the CTD group (50.0% vs. 37.2%, respectively; P=0.00052). It should be noted that only 67% of patients included in the trial actually received HDT. Logistical regression analysis revealed that CTD as an induction regimen was a significant predictor of post-induction response (odds ratio 1.91; 95% CI 1.44–2.55; P<0.0001) when controlled for bisphosphonate regimen and minimization factor.
Within this study, in which there were no formal age criteria for exclusion, we saw a significant impact of age on OS where, according to a cut-point analysis, the median OS [95% CI] differed for patients aged 55 years or younger (not reached [NR]; [63-NR]; range 0–74 months), those aged 56–64 years (63 months; [59-NR]; range 0–73 months), and those aged older than 64 years (53 months; [45–69]; range 0–69 months) (Online Supplementary Figure S1). The assumption of no treatment interaction for both PFS (P=0.71) and OS end points was valid (P=0.74), and CTD was non-inferior to CVAD for PFS and OS. In the per-protocol analysis, the median PFS [95% CI] was 27 months ([24–29]; range 0–73 months) in the CTD group and 25 months ([23–26]; range 0–72 months) in the CVAD group (HR 0.94; [0.81–1.09]; P=0.56) (Figure 2A). OS was comparable in both treatment groups (median NR; [61-NR]; range 0–74 months vs. median 63 months; [59-NR]; range 1–73 months; HR 0.92 [0.75–1.13]; P=0.29) (Figure 2B).
In the subset of patients who received ASCT and were treated per protocol, the median PFS (95% CI) was 34 months (31–37) in the CTD group and 33 months (29–36) in the CVAD group (HR 0.90; [0.74–1.10]; P=0.56). OS was comparable in both treatment groups (median NR; [NR-NR] vs. median NR; [67-NR]; HR 0.82 [0.61–1.12]; P=0.20). The 33% of patients in the study who did not proceed to HDT/ASCT and who were progression-free after one year had a median PFS of 25 months (95% CI 21–29); those who were alive at one year had a median OS of 50 months (95% CI 46–63). After adjustment for age, these outcomes were identical to those for elderly patients treated in the non-intensive pathway of the MRC Myeloma IX study.19
To determine the influence of response on outcome, we compared PFS in patients who achieved a CR following ASCT with that in patients who achieved less than a CR (VGPR, PR, MR, or no change) regardless of treatment group. As expected, PFS was greater in patients who achieved a CR (median 39 months; [95% CI 35–43] vs. 32 months [95% CI 29–35]; P=0.0099) (Figure 3A). Analysis of OS in responding patients only showed a borderline benefit for the CTD group (P=0.10; Figure 3B). Given this substantial, and highly significant, improvement in CR rates in the CTD arm, we hypothesized that, with prolonged follow up, this would inevitably translate into improved OS. We modeled this by concatenating and combining PFS durations and survival after relapse for the different response subgroups to produce predicted OS curves (data not shown). From these it became clear that, based on the improved CR rate and its associated PFS benefit in the CTD-treated patients and with further follow up, the survival benefit would likely increase, equating to a 3% improvement in survival at nine years. This 3% improvement, although small, is clearcut as it results from the longer-term improvement in CR rates combined with the longer PFS duration in patients achieving a CR, and is an approach that could be used in other studies to understand the impact of improved response rates on survival.
Results from FISH were available for approximately half of all patients (Online Supplementary Table S1). Overall, 293 patients had "adverse" interphase FISH (152 CTD and 141 CVAD) and 333 patients had "favorable" interphase FISH (167 CTD and 166 CVAD). In patients with favorable interphase FISH, median PFS was 34 months with CTD (95% CI 27–38; range 0–73 months) and 32 months with CVAD (95% CI 25–38; range 0–72 months; P=0.90) (Figure 4A). Median OS was NR with CTD (95% CI NR-NR; range 0–74 months) and NR with CVAD (95% CI 62-NR; range 0–72 months), but there was a trend for emerging survival benefit (P=0.11) with CTD (Figure 4B). In patients with adverse interphase FISH, PFS and OS outcomes were similar regardless of the type of induction therapy used (PFS 20 months with CTD vs. 18 months with CVAD, and OS 45 months with CTD vs. 46 months with CVAD) (Figure 4C and D). Among patients who achieved CR after induction therapy (regardless of regimen), patients with favorable interphase FISH had significantly better PFS (P<0.0001) and OS (P=0.0017) than those with adverse interphase FISH (Online Supplementary Figure S2).
The median number of cycles of induction therapy delivered was 5 (range 0–9) for CTD and 4 (range 0–8) for CVAD. The dose of thalidomide was reduced in 29% of patients. Although 749 patients (67%) went on to receive HDT with ASCT, 362 patients did not receive any part of the HDT-with-ASCT regimen. Reasons for this included: patient not fit/clinician's decision (129 patients), death (93 patients), patient's decision (29 patients), and inadequate stem-cell collection (15 patients).
The incidence of severe cytopenias and infection was higher in the CVAD group than the CTD group, whereas grade 3 constipation and somnolence were more common in the CTD group (Table 3). Increased alkaline phosphatase levels were recorded in 18% of patients in the CVAD group and 16% of patients in the CTD group. The incidence of renal insufficiency or failure was similar in both treatment groups (3.2% CVAD and 3.6% CTD), and the incidence of hypothyroidism was low in both treatment groups (<1%).
A total of 208 thromboembolic events were recorded: 116 events occurred in 100 patients randomized to CVAD and 92 events occurred in 86 patients randomized to CTD (P=0.30; Online Supplementary Table S2). As expected, central-line events were more common with the infusional CVAD regimen than the orally administered CTD regimen (39 vs. 5 events). No other pattern was discernible, in particular regarding the incidence of deep-vein thrombosis and pulmonary embolism. There was an early-mortality rate of 8.5% which did not differ between the CVAD and CTD arms (9.4% vs. 7.4%, respectively; P=0.28 Fisher's exact test). Overall, 217 patients in the CVAD group died versus 195 in the CTD group (P=0.19). The most common causes of mortality related to myeloma or its treatment were: disease progression, infection, renal failure, and transplant-related mortality. Three deaths in the CVAD group and 4 in the CTD group were attributed to VTE. The increased number of deaths in the CVAD group was attributable mainly to an increase in fatal episodes of renal failure and myeloma-related infections. During HDT and the peri-transplantation period, a transplant-related mortality rate of 1.5% was seen that was independent of the induction pathway followed (1.6% [6/379] CVAD vs. 1.4% [5/370] CTD; P=1.0 Fisher's exact test).
This study shows that CTD induction therapy improves both overall response rates and CR rates, compared with CVAD, and provides comparable PFS and OS. The post-induction overall response rate (≥ PR) of 82.5% (CR rate of 13.0%; ≥VGPR rate of 43.2%) achieved with CTD compares favorably with previous studies, in which thalidomide-dexamethasone induction regimens (with or without doxorubicin) produced overall response rates of 63–79% and CR rates of 3–10% (≥VGPR 19–44%).3,4,9,11–14,23 The results are also similar to those achieved with bortezomib-or lenalidomide-containing regimens, which have produced post-induction response rates of approximately 79–93% and ≥VGPR rates of 32–62%.23–26 Although of interest, it must be taken into consideration that these are not direct, randomized comparisons and will reflect differences in methodology, such as response assessment, number of ASCTs, number of treatment cycles given, and characteristics of patients entered. In this study, 10.4% of CVAD patients and 16% of CTD patients became immunofixation negative after induction therapy, and 40.9% and 55.1%, respectively, were immunofixation negative post high-dose therapy. CR was confirmed by bone marrow aspirate in 92.1% of immunofixation-negative patients after HDT and 98.8% of immunofixation negative patients post-transplantation where a bone marrow sample was available. These data indicate a strong correlation between negative immunofixation and less than 5% of plasma cells on bone marrow analysis.
In the CTD treatment group, CR rates increased from 13% post-induction to 50% among patients who received HDT with ASCT. It should be noted that only 67% of patients included in the trial actually received HDT. Although response rates may vary if the intent-to-treat population was used, this increase in the CR rate is particularly encouraging as we show in our subsequent analyses that patients achieving CR have an improved survival outcome. CTD seems to correlate with improved responses compared with thalidomide plus dexamethasone, and with reduced toxicity compared with thalidomide plus dexamethasone and adriamycin. The IFM has shown that bortezomib and dexamethasone (VD) is associated with better responses than VAD, with CR/near-CR rates of 15% vs. 6%, respectively.25 The addition of a third agent to VD improves the post-HDT response rates, with CR rates of 21% with bortezomib, doxorubicin, and dexamethasone (PAD), 38% with bortezomib, thalidomide, and dexamethasone (VTD), and 22% with cyclophosphamide, bortezomib, and dexamethasone (CVD) regimens.23,27,28 The CR rates were 50% with CTD, which is in the same range as those obtained with those regimens; however, exact comparisons will require formal randomized studies.
An improvement in CR rate was noted after ASCT in both arms of the study, with an increase in CR rate of 29.1% in the CVAD arm and 37.0% in the CTD arm. This observation illustrates the importance of high-dose melphalan in improving response rates even when the induction is given to maximum effect.
Overall, the CTD regimen was associated with median PFS and OS values that were not statistically significantly different to those achieved with the CVAD regimen, although the CTD curve was above the CVAD curve. Despite not using an age cut off, and having a high median age (59 vs. 55 years in the prior MRC Myeloma VII study), the PFS and OS results between arms are comparable.2 Survival analyses indicate a trend toward a late improvement in OS favoring the CTD group, and this may become more obvious with further follow up, as has been seen in a previous study.29 In the MRC Myeloma IX study, the principal analyses have been planned to include a further analysis at the 6-year median follow-up time point.
Cytogenetic classifiers can be used to define groups of patients with distinct biology and clinical outcomes; currently, however, only limited data are available on the impact of cytogenetic abnormalities on outcomes in patients undergoing induction therapy for MM. An important result of this study is the significant difference between treatment outcomes depending on the biological subgroup, as defined by FISH, into which the patient falls. Consistent with previous work, we have defined adverse FISH as gain(1q), del(17p), t(4;14), t(14;16) and t(14;20), and favorable FISH as the remainder; in addition we have incorporated del(1p32) as a high-risk factor in younger patients.30 We show that response rates are very similar in the favorable and adverse FISH groups but despite this, there are clear differences between the two risk groups. Median PFS was 33 months in patients with favorable interphase FISH (95% CI 27–37; range 0–73 months) and 19 months in patients with adverse interphase FISH (95% CI 17–21; range 0–70 months; P<0.0001). Median OS was NR in patients with favorable interphase FISH (95% CI NR-NR; range 0–74 months) and 45 months in patients with adverse interphase FISH (95% CI 38–56; range 1–74 months; P<0.0001). Furthermore, we show that, in the group with favorable interphase FISH, there was a trend for improvement in OS for patients receiving thalidomide induction, where there were no effects for those with adverse cytogenetics. In addition, for patients in CR, adverse interphase FISH remains a predictor of poor PFS and OS. These results suggest that the group benefiting from the introduction of thalidomide into the induction therapy of younger patients with NDMM is defined by favorable biological characteristics, identified by their FISH subgroup. Altogether, these findings underscore the need for the incorporation of FISH analysis into the assessment of patients for entry into trials and for the routine management of these patients.
Although the induction regimens evaluated in this study were associated with similar rates of adverse events, the spectrum of events differed. Compared with CVAD, CTD was associated with a higher incidence of severe constipation and somnolence, which is consistent with the known toxicity profile of thalidomide. Notably, the CTD regimen was associated with less myelosuppression than CVAD and this may have contributed to the reduction in fatal cases of infection, facilitated stem-cell collection, and reduced hospital admissions.31
In summary, we found that CTD achieves better response rates and is not inferior compared with CVAD in terms of OS and PFS. In subgroup analyses, a significant survival benefit was observed in patients who achieved a CR and had favorable interphase FISH. Based on these results and comparing an oral to infusional regimen with significant negative impacts on patient lifestyle, which has a substantial risk of myelopsuppression, CTD offers an effective alternative induction regimen associated with improved response rates that is not inferior to CVAD and may have additional benefits in favorable biological subgroups.
The authors would like to thank all the patients, investigators, and staff at the participating centers who made this study possible. We are indebted to staff at the Clinical Trials Research Unit, University of Leeds, for trial coordination, data management and analysis; the Department of Immunology, University of Birmingham; Wessex Regional Genetics Laboratory, University of Southampton; Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals NHS Trust; and Institute of Cancer Research, London, for central laboratory investigations. The authors also thank the MRC Leukaemia Data Monitoring and Ethics Committee, the MRC Leukaemia Trial Steering Committee, the NCRI Haematological Oncology Clinical Studies Group, and Myeloma UK.
The following Principal Investigators (listed in alphabetical order according to city) participated in the study: Aberdeen – J. Tighe (Aberdeen Royal Infirmary); Abergavenny – N. Parry-Jones (Nevill Hall Hospital); Airdrie – I. Singer (Monklands District General Hospital); Aylesbury – R. Aitchison (Stoke Mandeville Hospital); Bangor – J. Seale (Ysbyty Gwynedd); Barnsley – D. Chan-Lam (Barnsley District Hospital NHS Trust); Barnstaple –C. Rudin (North Devon District Hospital); Basildon – P. Cervi (Basildon Hospital); Bath – C. Singer (Royal United Hospital NHS Trust); Birmingham – M. Cook (Queen Elizabeth Hospital), Y. Hasan (City Hospital), D.W. Milligan* (Heart of England Foundation Trust); Blackpool – M.P. Macheta (Blackpool Victoria Hospital); Bodelwyddan – C. Hoyle (Glan Clwyd Hospital); Bolton – M. Grey (Royal Bolton Hospital); Boston – V. Tringham (Pilgrim Hospital); Bournemouth – R. Hall (Royal Bournemouth Hospital); Bradford – L.J. Newton (Bradford Royal Infirmary); Bristol – R. Evely (Bristol Haematology and Oncology Centre); Bury St Edmonds – M. Karanth (West Suffolk Hospital); Cambridge – J. Craig (Addenbrooke's Hospital), A. Whiteway (Southmead Hospital); Canterbury – C. Pocock (Kent & Canterbury Hospital); Cardiff – H. Jackson (University Hospital of Wales); Carshalton – J. Behrens (St Helier Hospital); Cheltenham – S. Chown (Cheltenham General Hospital); Chester – E. Lee (Countess of Chester Hospital); Chesterfield – R. Collin (Chesterfield Royal Hospital); Chichester – P. Bevan (St Richard's Hospital); Colchester – M. Hamblin (Colchester General Hospital); Coventry – B. Harrison (University Hospital); Croydon – H. Lumley (Mayday University Hospital); Darlington – M. Mahmoud (Darlington Memorial Hospital); Dartford – A. Kamat (Darent Valley Hospital); Derby – A. McKernan (Royal Derby Hospital); Doncaster – B. Paul (Doncaster Royal Infirmary); Dorchester – A. Moosa (Dorset County Hospital); Dudley – J. Neilson (Russell's Hall Hospital); Dundee – K. Gelly (Ninewells Hospital); Eastbourne – J. Beard (Eastbourne District General Hospital); Edinburgh – H. Roddie (Western General Hospital); Epsom – L. Jones (Epsom General Hospital); Exeter –C. Rudin (Royal Devon and Exeter Hospital); Falkirk – R. Neilson (Falkirk and District Royal Infirmary); Gateshead – G. Summerfield (Queen Elizabeth Hospital); Gillingham – M. Aldouri (Medway Maritime Hospital); Glasgow – G. McQuaker (Glasgow Royal Infirmary), A. Morrison (Southern General Hospital), R. Soutar (Western Infirmary), P. Tansey (Victoria Infirmary); Gloucester – S. Chown (Gloucestershire Royal Hospital); Grantham – V. Tringham (Grantham and District Hospital); Great Yarmouth – S. Sadullah (James Paget Hospital); Grimsby – K. Speed (Diana Princess of Wales Hospital); Guildford – G. Robbins (Royal Surrey County Hospital); Harrogate – G. Bynoe (Harrogate District Hospital); Harrow – N. Panoskaltsis (Northwick Park Hospital); Hereford – L. Robinson (Hereford County Hospital); High Wycombe – R. Aitchison (Wycombe General Hospital); Hull – H. Sayala (Hull and East Yorkshire Hospitals NHS Trust); Ilford – I. Grant (King George Hospital); Ipswich – J.A. Ademokun (Ipswich Hospital NHS Trust); King's Lynn – P. Coates (Queen Elizabeth Hospital); Kingston upon Thames – Z. Abboudi (Kingston Hospital); Leeds – G. Cook* (Leeds Teaching Hospitals NHS Trust); Lincoln – K. Saravanamuttu (Lincoln County Hospital); Liverpool – P. Chu (Royal Liverpool University Hospital), B. Hammer (University Hospital Aintree); Llanelli – P. Cumber (Prince Philip Hospital); London – J.D. Cavenagh* (St Bartholomew's Hospital), N. Panoskaltsis (Central Middlesex Hospital); Manchester – D. Alderson (Trafford General Hospital), J. Cavet (Christie Hospital), J. Houghton (Hope Hospital), J. Yin (Manchester Royal Infirmary); Melrose – J. Tucker (Borders General Hospital); Merthyr Tydfil – W. Bashi (Prince Charles Hospital); Middlesbrough – A. Wood (James Cook University Hospital); Milton Keynes – D. White (Milton Keynes Hospital); Newcastle upon Tyne – G. Jackson (Freeman Hospital); North Shields – C. Tiplady (North Tyneside General Hospital); Norwich – M. Auger (Norfolk and Norwich University Hospital); Nottingham – N.H. Russell* (Nottingham University Hospitals); Nuneaton – M. Narayanan (George Eliot Hospital); Orpington – A. Lakhani (Princess Royal University Hospital); Paisley – A. Sefcick (Royal Alexandra Hospital); Plymouth – S. Rule (Derriford Hospital); Poole – A. Bell (Poole General Hospital); Prescot – J. Nicholson (Whiston Hospital); Romford – A. Brownell (Oldchurch Hospital); Rotherham – H.F. Barker (Rotherham District General); St Leonards on Sea – J. Beard (Conquest Hospital); Salisbury – J. Cullis (Salisbury District Hospital); Scarborough – A. Zaheer (Scarborough Hospital); Sheffield – J. Snowden (Royal Hallamshire Hospital); Sidcup – S. Bowcock (Queen Mary's Sidcup NHS Trust); Southampton – A. Smith (Southampton General Hospital); Southport – D. O'Brien (Southport and Formby District General Hospital); South Shields – M. Galloway (South Tyneside District Hospital); Stafford – P. Revell (Mid-Staffordshire General Hospital); Stockport – M. Haj (Stepping Hill Hospital); Stockton-on-Tees – Z. Maung (University Hospital of North Tees); Sutton – G. Morgan (Royal Marsden Hospital); Sutton-in-Ashfield – R. Faulkner (King's Mill Hospital); Swansea– S. Al-Ismail (Singleton Hospital); Swindon – N. Blesing (The Great Western Hospital); Taunton – S. Bolam (Musgrove Park Hospital ); Torquay – D. Turner (Torbay Hospital); Truro – A. Kruger (Royal Cornwall Hospital); Tunbridge Wells – D. Gillett (Kent & Sussex Hospital); Uxbridge – R. Kaczmarski (Hillingdon Hospital); Wakefield – D. Wright (Mid Yorkshire NHS Trust); Warwick – A. Borg (Warwick Hospital); West Bromwich – Y. Hasan (Sandwell General Hospital); Westcliff-on-Sea – P. Cervi (Southend General Hospital); Wirral – G. Galvani (Arrowe Park Hospital); Wolverhampton – S. Basu (New Cross Hospital); Worcester – S. Shafeek (Worcestershire Royal Hospital); Worthing – A. O'Driscoll (Worthing Hospital). *Member of the National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group.
A complete list of the members of the NCRI Haematological Oncology Clinical Studies Group appears in the Appendix
Funding: financial support for the MRC Myeloma IX trial was obtained from the NHS, NIH, UK Biomedical Research Centre at the Royal Marsden NHS Trust, Myeloma UK, and the Medical Research Council. Unrestricted educational grants from Novartis, Schering Health Care Ltd, Chugai, Pharmion, Celgene, and Ortho Biotech supported the trial coordination and the laboratory studies. None of the funding sources was involved in the study design, data collection, analyses, or interpretation. The authors received editorial support from Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation. Anna Georgieva, MD, PhD, provided editorial support. The authors were fully responsible for content and editorial decisions for this manuscript.
The online version of this article has a Supplementary Appendix.
Authorship and Disclosures
The information provided by the authors about contributions from persons listed as authors and in acknowledgments is available with the full text of this paper at www.haematologica.org.
Financial and other disclosures provided by the authors using the ICMJE (www.icmje.org) Uniform Format for Disclosure of Competing Interests are also available at www.haematologica.org.
- Received March 7, 2011.
- Revision received October 18, 2011.
- Accepted October 24, 2011.
- Copyright© Ferrata Storti Foundation


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JOOLA and North American Table Tennis (NATT) are excited to continue its Thanksgiving tradition of hosting the North American Teams Table Tennis Championships. For the third year running, the tournament will be held at the Gaylord National Resort in National Harbor, Maryland.
Located just across the river from the nation's capital, National Harbor features numerous restaurants, shops, nightlife, and access to downtown Washington, DC. Players and spectators have a plentiful selection of activities and experiences to choose from! With the success of this summer's JOOLA Teams South and JOOLA Teams West, we're expecting a large turn out and we're preparing prizes, raffles, and maybe even a pop-up shop! As players are busy with three days of intense competition, their families and friends can enjoy a multitude of fun activities! ICE!, an indoor winter wonderland featuring two million pounds of hand-carved ice sculptures and ice slides, will be right next door to the playing hall.
As the tournament approaches, registration is winding down with over 700 players split among 183 teams. Popularity of the teams format has risen among players because it packs a high quantity of matches and high quality competitors for each player. Teams of 3, 4, or 5 players compete with 3 players participating in any given team match. Team matches are Swaythling cup format: five matches out of nine. Each of the nine potential individual matches is a singles match played best three of five. Teams are seeded based on the combined rating of the three top players on the team and placed into preliminary groups. Each team will compete on the first day to place them in a division. Each division will consist of two groups with eight teams playing a round robin to determine who advances to the semifinals on Sunday afternoon. Two teams from each group will advance to compete for the division championship.
This year's tournament features the JOOLA White Super P 40+ Poly Ball so competitors will not be allowed to wear white while playing.
JOOLA North American Teams Championships 2015
November 27th-29th, 2015
Gaylord National Resort
National Harbor, Maryland
Find out more or register at joolateams.com
More About JOOLA
JOOLA was first established in Germany in the 1950s and quickly became a leading manufacturer of table tennis equipment. It gained international recognition by sponsoring several World Championships, and eventually became the table sponsor for the 1996, 2000, and 2004 Olympics. In 2006, JOOLA emerged onto the US table tennis scene with a vision to promote the sport of table tennis by providing the highest quality table tennis equipment to fit all table tennis lifestyles from the basement to the world champion player. JOOLA values its customers and relies heavily on customer feedback to create a wide variety of table tennis rackets, apparel, tables, and accessories for players, both professional and recreational. Today, JOOLA sponsors some of the world's most elite table tennis professionals and is proud to be the official table sponsor for the US Open and US National Championships. Partnering with USA Table Tennis (USATT), the national governing body for table tennis, North American Table Tennis (NATT), and the National Collegiate Table Tennis Association (NCTTA), JOOLA has grown its fan base to become the most visible table tennis brand in America.
Find out more at joolausa.com

subset: commoncrawl


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The Right to Vote!!!
On August 6, 1965, President Lyndon Johnson signed, the Voting Rights Act of 1965, which extended equal voting rights for African-Americans. As both White and Black non-violent supporters led by Dr. Martin Luther King Jr. fought for the right to vote in Central Alabama, today, you can trace their march toward freedom on the 54-mile trail and connect with their stories at the Interpretive Centers. Read More


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American Apparel is known for its racy advertisements and this time, they've gotten the Brits upset. Britain's Advertising Standards Authority (ASA) recently banned an ad by the racy company for being "overtly sexual" and "demeaning to women" — but the majority of you don't think it's that bad. 54% voted that the ad was "fine" while 46% said it was "way too sexy." Find out who thinks it's fine — and who thinks it's too sexy.
Source: SodaHead


text: Homaid Abdulla Al Shimmari is the CEO of Aerospace & Engineering Services at Mubadala Development Company. He drives the UAE's strategic vision for developing advanced industries, including the development of the country's aerospace sector. Homaid also holds prominent roles with key aerospace, communications technology, and defence organisations. An ex Lieutenant Colonel of the UAE Armed Forces, he holds a Bachelor of Science in Aeronautical Engineering from Embry Riddle Aeronautical University, USA.


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As the Seattle Storm aim for a season-high third straight victory, the team is looking into physical abuse allegations against leading scorer Natasha Howard.
With that cloud hanging over the club, the Storm visit the Minnesota Lynx on Wednesday night.
Howard, averaging team highs of 17.4 points and 8.2 rebounds, scored 14 in a 78-69 home victory over New York on Sunday. It was one day after her wife posted a video on Twitter dating back to March in which she was yelling at Howard about being threatened by the Storm's All-Star forward.
"We are in continued communication with the league, and their investigation is now in progress," the Storm said via a statement over the weekend.
While charges have not been filed, it would appear Howard will be ready to play Wednesday. It's apparently another moment of adversity for reigning WNBA champion Seattle (10-8), which has already dealt with coach Dan Hughes' cancer diagnosis and injuries to stars Breanna Stewart, Sue Bird and Jewell Loyd (15.8 ppg).
However, the Storm still have a winning record and will attempt to focus on a chance for a second win in three games with Minnesota (10-7) this season. Howard has totaled 30 points in two contests against the Lynx.
Minnesota leading scorer Odyssey Sims, who is also dealing with her own off-court issues while reportedly facing drunk driving charges from an incident earlier this season, had 15 points and Sylvia Fowles added 14 with 13 rebounds in Sunday's 75-62 home win over Phoenix. For Fowles, it was her league-record 158th double-double.
"The things that (Fowles) does, it's because she's so consistent with it that people don't acknowledge it as much as they should, but the passes that she catches, the things she can do, defensively, she can guard guards, I mean she can guard guards on the perimeter," rookie teammate Napheesa Collier, who had 14 points with 11 rebounds versus Phoenix, told the Lynx's official website.
Fowles has 23 points and 18 rebounds in the two games with Seattle this season. Sims, meanwhile, totaled 20 points in those two contests.
"It's (Sims) and Syl that sort of make our offense go," Minnesota coach Cheryl Reeve said.
Crystal Langhorne scored a team-high 19 points off the bench for Seattle against the Liberty.


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5 Problems in the Gambling Industry Solved by Blockchain
December 11, 2018
bitbook, gambling, ico
5 Problems in the Gambling Industry Solved by Blockchain
The blockchain technology is on its way to become a part of our daily lives. Big enterprises are implementing modern blockchain solutions in their businesses. However, there are industries in which the blockchain technology and cryptocurrencies can interact at a deeper level. Gambling is one of these industries.
The traditional online gambling platforms like casinos or games don't ensure transparency to their users. There are many doubts about the real results of the games, winnings of customers, personal data security and others. There are reasons why people give up playing or betting; they are not confident about these services anymore. With the implementation of blockchain, online gambling platforms can restore their trustworthiness, and, as a result, bring back new users. But how exactly can blockchain technology change gambling today?
Unsurpassed Growth of the Gambling Industry
The online gambling industry exploded into the market a few decades ago and has become a successful multi-billion dollar industry. Current gambling platforms provide access to various games and activities at the tip of your fingerprints. Online gambling is definitely at its peak, and statistics show the business and the number of users is growing rapidly. The main principle of online gambling is betting money or something valuable on activities as poker, casinos, sports, lotteries and other games online. According to the report made by Statista, the online gambling business had a volume of 37.91 billion U.S. dollars in 2015, and, according to forecasts, this will increase to 59.79 billion U.S. dollars by 2020. The numbers sound promising for the future of online gambling. What is more, the investigation made by BusinessWire has shown online gambling is legal in 80 nations. Europe is in first place in the online gambling market. The high incomes of users and special regulations allowing this kind of activity help European markets make about 47.78% in the global gambling industry. The Middle East and Asia share second place and have 30.79%, while Northern America has 12.9% of the global market.
Challenges Blockchain Overcomes
There's no lack of additional benefits like security and privacy for any business dealing with money. Blockchain technology can improve it through cryptography. In the traditional online gambling and betting platforms, the games are controlled by the owners, which allows them to change the results of the game. While information about the process of the game and the results are hidden from users, there's a question about the fairness of the game. The number of customers decreased because they didn't have access to game information and lost their trust in fair gambling platforms. However, blockchain solves this and many other problems existing in online gambling.
How Blockchain Disrupts the Gaming Industry
Currently, online players continue to face many concerns with online gaming sites, including data insecurity, the lack of information transparency, high fees in money withdrawing, and fraudulent activity. Below, we explain how blockchain overcomes these obstacles as well as the opportunities it brings to online gambling.
The lack of transparency and trust
Problem: People associate gambling with fraud. It was proven by the study conducted by the British Gambling Commission in 2017. Players think online gambling is far from fair because they believe online gambling platforms have special software able to change the result of a game or its process in the operator's favor.
Solution: Blockchain technology based online casinos or sportsbooks like Bitbook make their transactions transparent and accessible to every user. The gap between operators/owners and customers doesn't exist anymore. Players can begin to trust in fair gambling.
2) The possibility of fraud
Fraud and leakage of important information cause trouble in each industry through money or customer losses. Many online gambling platforms require the personal information of users, but they can't guarantee it is secure.
Solution: Security of information is what blockchain is about. First, the information stored in the blocks is hard to hack and change. The Bitbook company goes further because credit card information doesn't need to be kept on the platform. Players are required to share a minimum of their sensitive data to be used by the Bitbook's global online casino and sportsbook.
3) Long-awaited payments and additional fees
Withdrawing money on a credit card or bank account is not the best option because banks can confiscate money or block the transactions from gambling platforms, which leads to payment delays or other financial issues. Furthermore, in case of money withdrawal or bank operations, customers may need to pay commissions or unexpected fees. The transactions can fail or be impossible to process.
Solution: Modern online gambling platforms use various cryptocurrencies allowing fast operations and payments in comparison with fiat money. Cryptography technology ensures user security and privacy and exempts the possibility of money being blocked/confiscated by third parties and by limitations of money deposits. Also, cases of failed transactions and fraudulent activity are lower than before.
4) No rewards for customers
Players are not rewarded by casinos for their loyalty; in case they lose, they do not receive any sort of compensation. That's how traditional gambling businesses have lost their customers.
Solution: To keep users engaged, modern online gambling platforms return some money to players in accordance with their monthly losses or propose special bonuses for them. A unique feature of Bitbook is that the platform gives back its customers 10% of their losses back every month. This has become possible due to lower transactions costs with blockchain technology.
5) Anonymity
Casinos follow special regulations to make the process of registration, account creation and verification more difficult. Users are required to submit valuable personal data that is stored on the gambling platform, leaving it vulnerable.
Solution: Blockchain allows users to bet and play by sending cryptocurrencies to the provided address, and do not fear the possibility of their personal information being stolen. Anonymity is one of the best benefits blockchain has brought to the gambling industry.
Cryptocurrencies and blockchain-based technologies change the structure of online casinos and the way they work. Online gambling is reaching an entirely new level of transparency and credibility. Obviously, blockchain technology has become a powerful tool for solving problems in our society and economy. In the gambling industry, these problems have been strongly felt. Cryptocurrencies, cryptography and blockchain are the future of this sphere.


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Rice University
Office of Public Affairs / News & Media Relations
David Ruth
Amy McCaig
Study: Risk assessment tools may increase incarcerations rates
Number of incarcerated increased five times between 1972 and 2007
HOUSTON – (June 6, 2018) – The use of risk assessment tools has increased considerably within criminal justice institutions in recent decades, and these tools have been viewed by many as a way to stop or even reverse the United States' heavy reliance on imprisonment. But new research from a Rice University sociologist suggests these tools may actually contribute to expanding the number of people caught up in the criminal justice system.
"Theorizing the Performative Effects of Penal Risk Technologies: (Re)producing the Subject Who Must Be Dangerous" will appear in an upcoming edition of the journal, Social & Legal Studies. The paper by Robert Werth, a senior lecturer in sociology at Rice, draws on both empirical data and previous research and examines the effects of risk assessment tools within the parole system.
"In the United States today, there's a big debate going on about how to best reform criminal justice systems and reduce mass incarceration," Werth said. "In the realm of punishment, risk assessment tools are used to predict the likelihood of reoffending. They evaluate individuals on a number of factors, including past criminal behavior, age, education, etc. They are used to help determine parole and how closely or not closely to supervise people who are paroled."
In the paper, Werth suggested that risk assessment instruments are contributing to an environment that considers everyone who is assessed a risk, which in turn may lead to higher levels of people being caught up in the criminal justice system.
"While these instruments note variations in the amount or level of risk, at the same time they promote the idea that everyone in the criminal justice system is dangerous," Werth said. "Yet we know that a significant number of people are there for low-level, non-violent offenses and represent little or no threat to public safety."
Werth notes that as the use of risk assessment tools increased, so did the number of people imprisoned. In 1970, only one state – Illinois – used actuarial risk assessment tools for determining parole release from prison. During the 1970s, the federal government and California began using these tools. In the 1980s, six more states joined the list. By 2004, 28 of the 32 states with a parole system were using risk assessment tools as part of the parole decision-making process.
In 1972, there were approximately 375,000 people incarcerated in the U.S. By 2007, the number had climbed to 2.1 million people. In 1972 the incarceration rate was 161 incarcerated people per 100,000 residents, compared with 767 per 100,000 in 2007.
Last year the U.S. spent approximately $80 billion on prisons, Werth said. He hopes the research will shed light on how risk assessment tools may impact incarceration rates.
"It has been argued that risk assessment tools could help stem the tide of mass incarceration," Werth said. "However, the evidence suggests that thus far, risk assessment instruments have contributed to expanding the number of people enmeshed in the criminal justice system – encompassing imprisonment, probation and parole."
The research was supported by funding from Rice and the University of California, Irvine, and a grant from the National Science Foundation.
This news release can be found online at news.rice.edu.
Follow Rice News and Media Relations on Twitter @RiceUNews.
Related materials:
Robert Werth bio: https://sociology.rice.edu/robert-werth
Photo link: http://news.rice.edu/files/2018/04/werth-b-1h63prb.jpg
Photo credit: Jeff Fitlow
Rice School of Social Sciences: https://socialsciences.rice.edu/
Rice Department of Sociology: https://sociology.rice.edu/
Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,970 undergraduates and 2,934 graduate students, Rice's undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for quality of life and for lots of race/class interaction and No. 2 for happiest students by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/RiceUniversityoverview.


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John A. Pagliei, Jr., DMD in Jamison, PA
Looking for a comfortable, confident and convenient dental experience? You've come to the right place. We value our patient relationships, making it our priority to deliver gentle compassionate care that you deserve. We strive to develop lifelong relationships with our patients by combining the latest dental technology with a professional and compassionate staff. The result is a beautiful, healthy smile that lasts a lifetime.
We also believe that patients should have sufficient information to make educated decisions about their oral health and treatment options. You'll find all of this important information on our website, including directions to our Jamison office, service descriptions, patient forms, patient education resources and more.
We are a full-service practice providing for all of your dental needs. Our services include general dentistry, cosmetic dentistry, teeth whitening, crowns, preventive care or periodontal exams. Or you can browse our educational library, find directions to our office or even request an appointment.
New patients are always welcome. We're your neighbors and we're here to help you maximize the health of your smile.
Our Pledge To You is to provide excellent dental care, to help patients make informed educated decisions in a clean, friendly atmosphere, as well as…
- Help you feel relaxed and comfortable
- Personalize appointment times and treatments to your needs, NEVER rushed
- Always listen to your needs/concerns (NOT your insurance company's)
- Provide excellent restorative and cosmetic dentistry using only the BEST laboratory and state-of-the-art equipment
- Submit claims and help you work with insurance company to receive maximum benefits
At our office your care is NEVER based on what your insurance company says they will cover, your care is ALWAYS based on what is in your best interest and is ALWAYS your decision!


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The Computer Science and Mathematics Scholarship Program (CSM) is accepting applications now through February 15. Students accepted into the program receive support for professional development and career planning, which emphasizes collaboration and communication skills for success in the workplace.
Funded through a National Science Foundation grant, the program aims to increase the number of students earning undergraduate and graduate degrees in the fields of mathematics and computing.
To qualify, student must be enrolled full-time in a computer science, computing and management, and or mathematics degree program at the baccalaureate or masters level. In addition, students must have a 2.8 grade point average or higher; be a U.S. citizen, national, permanent resident, or refugee; demonstrate financial need; and show completion of preferred course work. Applicants do not need to be enrolled at Lehman at the time of application submission, but the scholarship is awarded only to students admitted to the College and enrolled full-time for the upcoming semester.
Applications are available in the Office of Testing, Scholarships and Awards, located in Shuster Hall, Room 205. For more information about the scholarship, visit http://comet.lehman.cuny.edu/csmscholarships/.


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Staying healthy has become one of the biggest challenges that one has to face in the current world. Especially due to the constant busy schedules and lack of exercises, many seem to have witnessed deteriorating health at a younger age than it should happen. Therefore, it is highly important that you are aware of how important this element is to your life. Even at the old age, it is important not to feel weak, and it is the habits that you take now that will make an impact in the future. Here are some reasons as to why you should be concerned about your health at all times.
Being diagnosed with an illness or a disease is perhaps one of the scariest things that you have to face in your life. Therefore, it is up o you to gain control of your own life and keep you away from the facer of danger. Although some diseases are not always preventable, there are those that can be controlled and avoided due to good habits in your lifestyle and diet. If you wish to save yourself from such situations, it is always wise to turn to a lifestyle that promotes your physical health.
Mental wellbeing
While the physical wellbeing of a person is highly important, so is the mental condition of one's mind. If you do not find stability in your mind, there is difficulty in balancing out your life's tasks. Therefore, you need to pay attention in maintains the serenity in your head. This can be achieved by engaging in physical forms of exercises by attaining gym membership in Singapore and working out as well. However, the most effective forms will be Yoga and breathing exercises which will help you gain more control of your mind and its health.
The way you maintain your lifestyle will affect your health while your overall health will affect your lifestyle as well. Therefore, it is important to keep in mind that these two factors go hand in hand and create impacts on each other. In order to carry out a balanced lifestyle, you need to ensure that you engage yourself in exercise and cardio workouts at a gym or at home, so that your physical health will be at a satisfactory level.
In order to achieve success in life, it is important that you feel confidence within you. This is where the importance of health walks in once again, as you need to carry the feeling of confidence even in the aspect of health. The healthier you are, the more accomplished you will become.
Therefore, always be concerned of your health.


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Are you looking for a publishing job? Here are a few resources to help you.
Where to find publishing jobs
Twitter is a great place to keep an eye on the latest publishing jobs – but there are quite a lot of different sources to keep up with. Follow our @publishingjobs feed for links to a selection of the latest jobs from a range of recruiters and publishers.
LinkedIn is a great tool for your publishing job search. Keep your profile current, and relevant to the job you are looking for. Make connections and follow companies you'd like to work for. Join relevant groups – many include job postings. We also have a Publishing Talk LinkedIn group, which may incude some job ads in the future.
Here are 10 ways to use LinkedIn to find a publishing job.
Recruitment agencies
There are specialist recruitment agencies in the publishing industry. Keep an eye on these sites for their latest publishing jobs.
Publisher websites
If there's a specific publisher you'd like to work for, most publishers have their own online recruitment pages. Here are a few examples.
Job sites
In the UK, The Guardian regularly lists publishing jobs, and jobs sites such as indeed are popular worldwide.
Where to find careers advice
You can also find some careers advice on this blog, and other websites such as bookcareers.com. We sometimes post careers advice on Twitter at @publishingjobs too, and run Twitter-based career chats.
Here's some advice on using Twitter as part of your job search.
Where to advertise your publishing jobs
Are you recruiting? Get in touch if you'd like to see your job ads featured in our @publishingjobs Twitter feed or in our LinkedIn group.


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Do You Believe in Magick?
$5.00 – $20.00
How do you get someone to ask you on a date when you are a witch? Love potions? Magic charms? Maybe all it takes is a carefully dropped hint.
$5.00 – $20.00
How do you get someone to ask you on a date when you are a witch? Love potions? Magic charms? Maybe all it takes is a carefully dropped hint.
Jo Rake
12 minute comedy
3 women
About the play: Elsbeth really wants Robbie to ask her for a date but how do you do it when you are a witch? Love potions? Magic charms? Sisters Maryann and Sarita are no help at all. Or are they? Maybe all it takes to get a date is a carefully dropped hint.
About the playwright: Jo Rake's first theatre role was as Mary in a first grade Nativity play. More interested in singing and dance, it took many years before Jo found her way back to the stage but she has been a theatre devotee ever since, both on the stage as an actor and behind the scenes as director, stage manager, costumer, board member and performance judge. Jo is a founding member of a Senior Theatre company that tours performances to senior residences and living centers. She began writing plays for the company using the antics of her family and neighbors as well as just her imagination as inspiration. In 'real life.' Jo is a mostly retired CPA.
Do You Believe in Magick? was first performed by The Hourglass Players at The Atria at the Arboretum in Austin, TX.
See Jo Rake's other plays: G-O-A-L, Anniverary, and For… Press or Say…
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Jo Rake
|Running Time
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*August 7 - 13
|SABBATH AFTERNOON August 7
Read for This Week's Study:
|Matt. 5:13-16, 22:15-21, Acts 5:29, Rom. 13:1-5, 1 Pet. 2:13-15.
Memory Text:
| "Therefore, it is necessary to submit to the authorities, not
only because of possible punishment but also because of conscience"
One of the greatest questions facing the church is the issue of political involvement. How do people in the world but "not of the world" (John 17:14) relate to the political challenges presented by the world? History is replete with examples of churches that have kept silent during times of great moral and political crises; history, however, also bears a sad witness to what happens when churches take upon themselves political prerogatives that place them decidedly upon the side of evil.
This week we look at the complex and often difficult question of how Christians are to relate to the political issues of the day. Because Christians exist in all sorts of political environments, we can look only at broad principles; in fact, the Bible gives us only broad principles. Perhaps that's because the Lord, knowing the various and often delicate situations His people would be facing through the centuries, revealed principles broad enough to be used in any environment.
The Week at a Glance:
|What kind of influence should Christians have in society? How should Christians relate to the political process? Should Christians be in government? What principles should we follow in seeking to balance our obligations as citizens with our obligations to the Lord?
*Study this week's lesson to prepare for Sabbath, August 14.
August 8
Sanctified Caution (Matt. 5:13-16).
Many Christians believe we should give up on the world. The world is so evil, so confused, and so estranged from God's original purpose that there is no hope of turning the situation around. Plus, the more we are involved with the world, the greater the chances we will become even more contaminated by it. Withdrawal is the only option for those who want to remain faithful to the Lord. This argument may sound plausible, but is it biblical?
What role does God expect a Christian to play in society? Matt. 5:13-16
Christians must do all they can to make a difference in society. They are called to give a more pleasant taste to the world around them and to provide spiritual light. As someone once said: "It is better to light one candle than to curse the darkness!"
In early Adventism, the question was often asked whether it would be right for an Adventist Christian to go to the ballot box. Today, most Seventh-day Adventists do recognize that it is their privilege to cast their vote in democratic elections and referendums in an attempt to help promote an agenda that is closest to upholding kingdom values. How we do this, of course, isn't always easy; much depends not only upon our political and social environment, which can vary greatly from country to country, but also on what individual members believe regarding which agenda best upholds kingdom values. Because these questions can be so fraught with many potential hazards, as believers we should always proceed with sanctified caution when it comes to dealing with social and political issues.
How do you balance the verses quoted above in Matthew with texts such as 2 Corinthians 6:17 or James 4:4?
|The issue for most Christians isn't that we should seek to better whatever society we find ourselves in, but rather, How do we best do that in a way that doesn't compromise our witness or our obligations to the Lord? As with so many things, we need to strike a correct balance, which is not always easy. At such times, when these questions can have a very powerful impact for good or evil upon the church or upon society as a whole, members, more than ever, need to seek the guidance of the Lord and the counsel of others in how to best proceed.
August 9
Christians in Government?
Imagine your nation is overrun by a foreign power that occupies your land, defeats your army, kills thousands of civilians, levels numerous cities, and takes many prisoners. Imagine, next, that one of those prisoners not only becomes a favorite of the very ruler who destroyed your nation but actually serves that ruler faithfully for many years. Most people would deem this person a traitor, would they not?
Who is the Bible character described above?
The answer, of course, is Daniel (see Daniel 1; 2:48, 49), whose story (among those of others) raises all sorts of interesting questions regarding the role of faithful people who are in positions of political power and authority.
What other biblical hero became a powerful political figure? Gen. 41:41-44.
Though, no doubt, the world of politics offers many potential pitfalls for any Christian, there have been those who have faithfully served in government positions. Indeed, even in our own church, Seventh-day Adventists have been involved in government. For a number of years a Seventh-day Adventist Christian served as the prime minister of Uganda. In Papua New Guinea, Seventh-day Adventists form a sizable percentage of the population, and, thus, it should not surprise us that there are many church members in high government positions. The same is true for several of the small island states in the Pacific. And even in countries where Adventists are less numerous when compared to the size of the population, we now find Seventh-day Adventists as members of Parliament or in other high positions.
|Think about this We believe God's law is a transcript of His character, that is, the law He has given us reflects the kind of God He is. With this idea m mind, why would we be better off living in a nation where Christians are involved in the political process, the very process that originates the laws of the country" At the same time, what potential dangers arise from those who seek to use government power to promote a religious agenda?
August 10
Obedience, Yes . . . But (Acts 5:29, Rom. 13:1-5).
Read Romans 13:1-5 and 1 Peter 2:13-15. What attitude toward political leaders do they admonish Christians to have?
Read Acts 5:29 and Romans 13:7. How do these verses help us better understand the texts quoted in the previous question?
There's no question that Christians, in whatever land they are in, should be good citizens, obeying the laws of their country. At the same time, as followers of the Lord, they answer to a higher Power, One greater than the government, to whom they are to give all due honor and respect, tribute, and custom (see Rom. 13:6, 7). At the same time, we must not forget that Paul and Peter died at the hands of the very authorities they were telling their people to obey. Obviously, then, respect for authority and obedience to the government have their limits.
Indeed, one powerful example comes from the history of the United States. In the nineteenth century, when the issue of slavery was dividing the Christians in the United States, Ellen G. White made it no secret as to where she stood.
"When the laws of men conflict with the word and law of God, we are to obey the latter, whatever the consequences may be. The law of our land requiring us to deliver a slave to his master, we are not to obey; and we must abide the consequences of violating this law. The slave is not the property of any man. God is his rightful master, and man has no right to take God's workmanship into his hands, and claim him as his own."Ellen G. White, Testimonies for the Church, vol. 1, pp. 201, 202.
|Throughout the years, there have been many examples of civil disobedience, of people purposely violating the law of their land in order to bring about political change. What potential dangers await Christians who get involved in such action? At the same time, what situations might exist where their Christian duty demands they get involved?
August 11
Paying Taxes (Matt. 22:15-21).
Few people, if any, like to pay high taxes. But in any modern society, the state must have large amounts of money to pay for the things a government is expected to provide: education, basic health care, roads, tunnels, bridges, police, armed forces, and so on. We may question whether the taxes should be as high as they often are, but we cannot question the legitimacy of being taxed.
What did both Jesus and Paul say about the legitimacy of taxation by the authorities? Matt. 22:15-21; Rom. 13:6, 7.
The tax referred to in Matthew 22 was "payable into the imperial exchequer, imposed on every inhabitant of the country from the time of puberty until the age of sixty-five. It was resented by the Jews as a repeated reminder of the fact that they were subject to foreign power in their own land.
"The attitude to the payment of taxes remained a moot issue in the early church. Paul finds it still necessary, nearly thirty years later than this, to lay down the rule for Christians. The authority of the state is divinely ordained, and the payment of taxes is to be made 'for the sake of conscience.' "Francis Wright Beare, The Gospel According to Matthew (Oxford, Eng.: Basil Blackwell, 1981), p. 439.
What other principle comes into play when we deal with our taxes? Luke 16:10-12, 2 Cor. 13:7.
We must show honesty and integrity in all our financial dealings. This principle also extends to what we can receive from or must pay to the government. It is dishonest to claim a benefit to which we are not entitled, and it is just as wrong to withhold from Caesar what is his due.
Of course, we may use all legitimate means to lower our taxes. But making false claims and defrauding the government are as much a dishonesty as stealing from our employer or from our neighbor. A Christian cannot be expected to smile when his or her taxes are higher than expected, but he or she can be expected to be honest.
|Suppose you have cheated on your taxes in the past. What can you do to make restitution?
August 12
Promoting Christian Values
The Seventh-day Adventist Church always has been strongly opposed to any interference by the state in the affairs of churches and other religious communities and, vice versa, the meddling by organized religion in matters of government. Individual members may choose to serve their country in a high office, but the Adventist Church believes that, as a corporate body, it should stay away from politics.
This does not mean, however, that the church has no interest in the values that are promoted in society and that it should not make its voice heard on moral issues that affect society. It would be wrong to impose some of our values on others, but it would be equally wrong not to present a strong witness with regard to the values we believe would make the world a better place in which to live. It is not always an easy balance to find.
What examples can we find in the Bible of faithful followers of the Lord who sought to bring about a change in government policy?
Besides these examples, the Bible, particularly the Old Testament, is filled with examples of the prophets attempting to influence government policy; that is, to try to get the rulers to turn away from apostasy and to follow the Lord. Of course, the times back then were radically different from any we face today. Nevertheless, there's nothing wrong with Christians seeking to use their influence toward helping bring about positive moral and social changes. The difficult questions arise, however, concerning just what changes a church should seek to bring about and how a church should implement these changes. Not everything that's sinful should be made illegal, a distinction Christians in all ages have not always understood. Where to draw the line has been and still is a difficult question for the church to answer. Thus, as mentioned earlier, this is a topic in which sanctified caution must be used.
What have been your own attitudes toward church involvement in politics? Do you tend to be an aggressive advocate of involvement, or do you think the church should shy away from these issues? What reasons do you have for the position you take?
August 13
Further Study:
|"Christ's reply was no evasion, but a candid answer to the question. Holding in His hand the Roman coin, upon which were stamped the name and image of Caesar, He declared that since they were living under the protection of the Roman power, they should render to that power the support it claimed, so long as this did not conflict with a higher duty. But while peaceably subject to the laws of the land, they should at all times give their first allegiance to God."Ellen G. White, The Desire of Ages, p. 602.
Discussion Questions:
| Ellen White was very active in the temperance movement
in the United States. In fact, she was so strongly in favor of banning alcohol
(prohibition) that she encouraged people to vote for prohibition-even if
the vote was held on Sabbath." 'Shall we vote for prohibition?' she asked.
'Yes, to a man, everywhere,' she replied, 'and perhaps I shall shock some
of you if I say, If necessary, vote on the Sabbath day for prohibition if
you cannot at any other time.' "A. L. White, Ellen G. White: The
Lonely Years (Washington, D.C.: Review and Herald Pub. Assn., 1984),
vol. 1, p. 160. Discuss the implications of her stance in the context of
this week's lesson.
Is it legitimate, or even a duty, for the church to speak out on some moral issues, even if this may draw the church into a political debate?
Though living at a time of great political corruption, Jesus said very little about the political issues of His day. What lessons can we draw from His example? What lessons should we not draw from that example?
|Christians are citizens of the heavenly kingdom first, but they are most definitely also citizens of their own country and are to accept their part of the responsibility all citizens should share. The principle of rendering to Caesar what is his and to God what is God's gives us a broad outline from which Christians are to work in whatever land they reside.
|I N S I D E Story
|Two-Banana War
by BONNIE NORTON and TREVOR ROBINSON
Two-Banana War
Too often it takes very little to start a war, and in the highlands of Papua New Guinea, it took only two bananas. When two Adventist pilots flew into an isolated village in the highlands of PNG, they discovered almost the entire village burned to the ground. Slowly they pieced together the story.
About two weeks earlier two friends from the village had gone to Port Moresby, the major city on the southern coast. One man had two bananas, but the other man had brought nothing to eat. In the morning Friend A awoke to discover one of his bananas was missing. Friend B denied having taken the banana, but Friend A was not convinced. In his mind he vowed that he would get revenge for the stolen banana.
The night that the two men returned to their village, Friend A sneaked out and set Friend B's hut on fire. The grass-mat sides and grass roof erupted into a ball of flame and burned to the ground in minutes. Thankfully, no one was killed. But Friend B knew who had done this and he vowed revenge.
The next night Friend B set Friend A's hut afire. Friend A called his clan members together, and that night they set fire to all the huts that belonged to Friend B's clan. In turn, Friend B and his clan set fire to clan A's huts. The remaining villagers could not stand to watch the excitement, so they took sides. Friend A's supporters set fire to Friend B's supporters' huts, and Friend B's supporters set fire to Friend A's supporters' huts. Soon nothing was standing except the little Adventist church.
Even the church seemed doomed when a man ran toward it with a burning torch in his hand. Then suddenly the man tripped and fell. He landed on a sharp stick poking out of the ground. The raging villagers stopped in their tracks. "God is watching out for His church!" they cried. "Which one of us would dare set fire to God's church?"
And so, if you fly into that village today, you will see our lone little Adventist church standing amidst a burned-out village. It stands as a reminder that amidst human frailties and passions, God stands waiting to change hearts and lives into the likeness of His Son.
BONNIE NORTON lives in Goroka, Papua New Guinea, with her husband, Adventist Aviation Services pilot Bill Norton. TREVOR ROBINSON works as a nurse at Sydney Adventist Hospital and is a missionary pilot in his free time.
|Produced by the General Conference Sabbath
School and Personal Ministries Dept.
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text: Master's Degree in Electrical Engineering from the University of Johannesburg, as well as an MBA from the University of the Witwatersrand in South Africa, and is a registered Professional Engineer. Joined ABB in South Africa in 1997. In 2007, he was appointed Country Manager for ABB in Qatar, Moving to Singapore in 2011, leading the Power Systems division in Southeast Asia. Since 2015, he has been been responsible for leading ABB in Singapore, as well as overseeing ABB operations in Bangladesh, Laos, Myanmar, Thailand, Indonesia, Vietnam, Malaysia and the Philippines.


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|Biosequences .. Software .. Molbio soft .. Network News .. FTP
Well I've finally managed to get a subtree drawn. I saved the subtree from Treetool in Newick format, edited the resulting treefile so that Treeview would read it, and then saved it as a PICT file. However I still have the problem with Treetool (Linux version) crashing every time I use the merge node command. Cheers, Bob Forster Centre for Food and Animal Research Ottawa, ON forster at em.agr.ca


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When MedStar Health executives decided to switch to Cerner's electronic health record (EHR), they knew it would be a challenge that ultimately would improve care by lowering time in the EHR, enhancing documentation and providing one unified record across all of MedStar's systems across Maryland and the Washington D.C. area. A total of 43 different specialties, 6,200 users and 465 ambulatory practices across MedStar adopted the new EHR, named MedConnect.
An implementation pilot program began in August 2016, followed by three larger waves of implementation. "We really went to being up and active in about a 12-month period," said Brendan Furlong, MD, vice president and chief medical information officer, MedStar Medical Group.
Providers quickly adapted to MedConnect. In January 2017, ambulatory providers signed more than 800,000 orders and completed 36,900 notes in electronic physician documentation solution Dynamic Documentation™ at its clinics.
"The biggest successes really have to do with individual doctors cutting significant amounts of time off their documentation in the MedConnect chart. That translates into more time the doctor can spend with the patient, and less time working during off hours," said Furlong.
At the start of the pilot program and each wave (August, September, November, and December 2016), physicians spent an average of six minutes and 36 seconds in MPages® chart review. After receiving help from adoption coaches, that dropped to an average of five minutes and 44 seconds.
This allowed physicians to see more patients. While they saw an average of 149 patients per month before coaching at implementation, they saw an average of 163 patients monthly after the coaching.
An optimization project that started in February 2017 helped save even more time. From February to June, the time in the chart dropped each month, with an overall 11 percent decrease. The optimization also saw a 19 percent decrease in orders time per patient for the same time period.
"The rollout was ultimately about coming together as a company with a unity of purpose," said Furlong. "We had a job to do; we had to get it done. Our clinician community, the clinician leadership, our information system and ultimately the Cerner partnership really made this job happen."


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Auswork.com is engaged in sourcing professionals to work in Australia or immigrate to Australia
Based on your credentials a Registered Migration Agent will make an initial assessment of the various possible pathways suitable for you to work in Australia or immigrate to Australia.
Connect with prospective employers or recruiters if you have the right credentials and require employer sponsorship, employer nomination, job offer for regional sponsorship or for overseas assignments.
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text: UC Berkeley & BERC are hosting Smogathon, an international competition for the best air pollution solution. Founded in 2015 in Poland, the country with the worst air quality in the EU, Smogathon has been attracting technological talent from the entire globe by offering cash prizes and funding for implementation. Apply by August 12 to compete in the North American semi-final in Berkeley on October 4. Winners will travel to Poland for the final and will have a chance to win at least $15,000 in cash plus implementation funding!


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Walinga USA, Inc.
Distributor of pneumatic conveying equipment and bulk feed transportation equipment.
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The Italian WAMGROUP, worldwide leader in developing and manufacturing equipment and plant components for bulk solids handling and processing
Warren Manufacturing celebrates 30 years in the bulk feed equipment manufacturing business in 2015!
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Since 1988 Weitl Aeration Service has been dedicated to repairing and restoring corrugated steel grain aeration tubing in the U.S.
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Wells Fargo Rail operates one of the largest, most diverse railcar and locomotive fleets of any rail equipment operating lessor in North America with over 175,000
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Wheatheart (AGI) was established in 1973 and offers portable grain augers including specialized self-propelled options, grain-handling accessories as well as, fencing equipment.
Manufacturer of precast concrete products such as Feedbunks, L-Panel and T-Panel for corn stroage, T-Fence and Cattle Guards.
WL Port-Land specializes in the storage, processing and handling of bulk materials in all industries.
Meyer & Sons, Inc., is a world leader in the manufacture of dry bulk material processing equipment, pneumatic conveyors, dust collectors, insulation blowing machines and vacuum collection systems.


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On a train with no ticket to Turkey, just 3000 miles to go to Goa.Read more »
From Vienna to Budapest – Hand to Mouth to India Chapter 3
Drunken antics win Tom a romantic week in Budapest as he continues to hitchhike to India.Read more »
Love and Betrayal in Budapest – Hand to Mouth to India Chapter 4
Sympathy for the hitchhiker as he gets seduced by a Hungarian beauty who runs the local cinema. All's fine until…Read more »
Curtains of Iron, Romania – Hand to Mouth to India Chapter 5
With chronic heartbreak and competition from a crowd of Romanian hitchhikers, the road gets rough and India seems a long…Read more »
Hand to Mouth to India by Tom Thumb – Hitchhiking to India – Out Now!
A young man's rite of passage and one hell of a travelogue.Read more »
Istanbul cops, Turkish Hooligans Serendipity – Hand to Mouth to India Chapter 7
How does a penniless hitchhiker find a bed? the Turkish cops are always ready to help.Read more »


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Real world construction for NZ's future engineers. Test your skill, logic and creativity.
Help young ones develop hand motor skills while creating 8 different models, including a Dump Truck, Crane, Excavator and Windmill.
They can build one of 8 models or, create their own! All 88 pieces including wheels, real hex tool and wrench can be conveniently stored in the plastic Toolbox so kids can carry the set anywhere they go! Construct a model Dump Truck or Excavator to make way for new developments! Rebuild the model as a Windmill, to generate power for your town! Easy to follow step-by-step instructions are provided so little hands can piece together large connecting pieces with Snap-On clipping screws and add on wheels.
- Create 8 different models from 88 pieces


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Firm Hand Spanking has one steamy hot update after another and one of the best spanking video libraries on the net! One of the recent Christmas presents Firm Hand has given us, is releasing a new series from their archives featuring Samantha Woodley. This former face of the site, plays a naughty cheerleader who gets her cute tushy spanked in many different positions and with many different implements. The "Cheerleader Challenge" series, adds to her already massive 240+ video archive.
Next I'd like to talk about the girl who is arguable the current face of Firm Hand Spanking. The lovely, glamorous, stunning, Dani Daniels has done her fair share of great spanking videos. When this vixen first became exclusive to Firm Hand Spanking she was strictly a top in her scenes. Then she started doing scenes as a bottom, but in my opinion they had more of a playful feel to them, than a feel of real punishment. Now she is also coming out with scenes in which her perfect bottom is receiving some harsh, and severe thrashings. On the 21st. of this month, a video is coming out that is being advertised as "our most dramatic video ever." I can't wait!
Nostalgia is the theme for Firm Hand recently. How about the return of the "What The Dickens" series with the lovely Amelia Jane Rutherford?
And lastly how about a decades old archive of Amber Pixie Wells. Her lovely creamy white bottom was made to be upended and spanked. David Pierson gives her the thrashing she deserves!


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How can I hear from God? What does God's voice sound like? Can I hear God's voice? Questions many of us ask ourselves, but unfortunately, don't find the answers to. Have you ever wished you could just sit down and have a long talk with the Lord? Wouldn't it be wonderful to move beyond having a theology that states that God loves you, and actually hear Him whisper words of love into your heart?
If you are one of His sheep, then He is speaking to you and you are hearing His voice! The problem is, most of us have not learned how to recognize His voice, and to differentiate it from all of the other voices that bombard our hearts and minds.
Featuring videos from Mark Virkler's 4 Keys to Hearing God's Voice, this course will teach you how to engage in regular dialogue with God. You will learn about biblical patterns for approaching God, how to distinguish God's voice from other voices that clamor for your attention, and how to record what God reveals using "two-way journaling."
We can teach you to hear God's voice. Contact us for more information on our next class.