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The use of third-generation aromatase inhibitors (AIs), such as anastrozole and letrozole, as initial adjuvant hormonal therapy in postmenopausal women (PMW) with hormone receptor-positive (HR+) breast cancer offers a significant benefit over tamoxifen for reducing recurrence risk. Clinical studies, including the Arimidex Tamoxifen Alone or in Combination (ATAC) and the Breast International Group (BIG) 1–98 trials, have proven that both anastrozole and letrozole are, respectively, superior to tamoxifen in improving disease-free survival. Although differing in design, objectives, and follow-up time, these trials offer some insight into the comparative clinical efficacy of these two nonsteroidal AIs. In particular, results from BIG 1–98 show that letrozole significantly reduces early distant metastatic (DM) events, which constitute the majority of early recurrence events. Subsequently, there is a beneficial overall survival effect emerging in the trial, whereas survival is unchanged with anastrozole after 100 months of follow-up in ATAC. Significant differences in the potency of these two drugs, vis-à-vis their degree of aromatase inhibition, have been observed in comparative trials and show that letrozole causes a more complete suppression of estrogen levels than does anastrozole. Whether this difference in potency is relevant to reductions in DM events during adjuvant therapy remains unclear. The Femara Anastrozole Clinical Evaluation trial is addressing this issue in a more unequivocal manner by comparing initial adjuvant treatment with anastrozole or letrozole in a population of breast cancer patients at high risk of recurrence: PMW with HR+ disease and axillary lymph node involvement.
anastrozole; aromatase inhibitors; hormone receptor-positive (HR+) breast cancer; letrozole; postmenopausal women; tamoxifen
Aromatase inhibition is the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease. The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and on the other hand, the irreversible aromatase inactivator exemestane. Although exemestane is the only widely used aromatase inactivator at this stage, physicians very often have to choose between either anastrozole or letrozole in general practice. These third-generation aromatase inhibitors (letrozole/Femara (Novartis Pharmaceuticals, Basel, Switzerland) and anastrozole/Arimidex (AstraZeneca, Pharmaceuticals, Macclesfield, Cheshire, UK)), have recently demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer improving disease-free survival. However, although anastrozole and letrozole belong to the same pharmacological class of agents (triazoles), an increasing body of evidence suggests that these aromatase inhibitors are not equipotent when given in the clinically established doses. Preclinical and clinical evidence indicates distinct pharmacological profiles. Thus, this review focuses on the differences between the non-steroidal aromatase inhibitors allowing physicians to choose between these compounds based on scientific evidence. Although we are waiting for the important results of a still ongoing head-to-head comparison in patients with early breast cancer at high risk for relapse (Femara Anastrozole Clinical Evaluation trial; ‘FACE-trial'), clinicians have to make their choices today. On the basis of available evidence summarised here and until FACE-data become available, letrozole seems to be the best choice for the majority of breast cancer patients whenever a non-steroidal aromatase inhibitor has to be chosen in a clinical setting. The background for this recommendation is discussed in the following chapters.
aromatase inhibitors; breast cancer; anastrozole; letrozole; exemestane
In 2005, results from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial ushered in a new era of endocrine therapy for hormone-responsive malignancies. This study demonstrated that, compared to tamoxifen (a selective estrogen receptor modulator [SERM]), anastrozole (aromatase inhibitor [AI]) prolonged time to recurrence and disease-free survival for postmenopausal women with breast cancer. The advantage was even greater for those with estrogen receptor-positive (ER+) tumors, and anastrozole was better tolerated than tamoxifen. Since then, AIs have become first-line adjuvant therapy for ER+ breast cancer in postmenopausal women.
In late 2010, a trial comparing abiraterone acetate (a 17-hydroxylase/17,20-lyase [CYP17A1] inhibitor) plus prednisone versus prednisone alone in men with castration resistant-prostate cancer (CRPC) previously treated with docetaxol chemotherapy was terminated early due to the survival benefit in the abiraterone acetate arm. This result not only validated a new therapy for CRPC but, with the antecedent phase I-II abiraterone studies, shattered our understanding of the molecular mechanisms underpinning CRPC development and progression.
AIs and CYP17A1 inhibitors will be widely used by oncologists, yet fellowship programs provide little training in steroid biosynthesis, compared with training in the biology of standard chemotherapies. Consequently, these drugs might be used without an appreciation of their caveats and pitfalls. The purpose of this review is to acquaint practicing oncologists with the fundamental principles and pathways of steroid biosynthesis, to improve their understanding of how and why these drugs work, and to alert these physicians to potential problems related to the drugs’ mechanisms of action.
For the upfront adjuvant therapy of postmenopausal estrogen receptor–positive breast cancer, the third-generation aromatase inhibitors (ais) have shown a more favourable overall risk–benefit profile than has tamoxifen. Benefits of the ais include less frequent gynecologic, cerebrovascular, and thromboembolic adverse events; greater disease-free survival; and lower tumour recurrence. Although approximately 25% of postmenopausal women with early breast cancer report experiencing symptoms of arthralgia with ai therapy, 68-month data from the Arimidex, Tamoxifen, Alone or in Combination trial showed that, compared with tamoxifen, anastrozole treatment was associated with only a modest increase in the incidence of joint symptoms. The events, which were mostly mild-to-moderate in intensity, led to treatment withdrawal in 2% of patients on anastrozole as compared with 1% in the tamoxifen arm. The symptoms and changes correlate with clinical, biochemical, and radiologic findings in symptomatic women. To determine appropriate intervention, it is therefore essential to perform a comprehensive evaluation of musculoskeletal complaints to distinguish natural menopause-related degenerative disease from ai-related effects. The present review explores the advantages of differential diagnosis with an emphasis on history and physical and musculoskeletal examination; laboratory investigations are used to corroborate or rule out clinical impressions. The transient symptoms associated with the ais are manageable with an appropriate combination of lifestyle changes, including exercise and joint protection in conjunction with pharmacologic approaches.
Arthralgia; arthritis; aromatase inhibitors; breast cancer
Results from the completed treatment analysis of the ATAC (Arimidex, Tamoxifen alone or in combination) trial indicated that anastrozole was significantly superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal women with hormone receptor-positive (HR+) early breast cancer. On the basis of these results, this study estimated the cost-effectiveness of anastrozole vs tamoxifen, from the perspective of the UK National Health Service (NHS). A Markov model was developed using the 5-year completed treatment analysis from the ATAC trial (ISRCTN18233230), as well as data obtained from published literature and expert opinion. Resource utilisation data and associated costs (2003–4 UK£) were compiled from standard sources and expert opinion. Utility scores for a number of health states were obtained from a cross-sectional study of 26 representative patients using the standard gamble technique. The utility scores were then inserted into the model to obtain cost per quality adjusted life-year (QALY) gained. Costs and benefits were discounted at recommended annual rates of the UK Treasury (3.5%). Modelled for 25 years, anastrozole, relative to generic tamoxifen, was estimated to result in 0.244 QALYs gained per patient at an additional cost of £4315 per patient). The estimated incremental cost-effectiveness of anastrozole compared with tamoxifen was £17 656 per QALY gained. There was a greater than 90% probability that the cost-effectiveness of anastrozole was below £30 000 per QALY gained and of the order of 65% that it was below £20 000 per QALY gained. The results were robust to all parameters tested in sensitivity analysis. Compared with commonly accepted thresholds, anastrozole is a cost-effective alternative to generic tamoxifen in adjuvant treatment of postmenopausal women with HR+ early breast cancer from the UK NHS perspective.
anastrozole; tamoxifen; aromatase inhibitor; breast cancer; cost-effectiveness analysis; cost-utility analysis
Endocrine therapy in the setting of breast cancer has undoubtedly advanced clinical outcomes in this disease, but treatment with endocrine therapy is accompanied by a wide spectrum of side effects. It is of prime importance to understand and characterize these toxicities to facilitate clinical decision-making. Somewhat surprisingly, there is a relative paucity of data pertaining to cognitive changes associated with endocrine therapy. In this article we review cognitive associated with two classes of endocrine therapy: (1) selective estrogen receptor modulators (SERMs; tamoxifen and raloxifene) and (2) aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane). Companion studies to the Multiple Outcome of Raloxifene Evaluation (MORE), the Study of Tamoxifen and Raloxifene (STAR) and National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trials provide relevant data to understand the effect of SERMs on cognition. In contrast, substudies of the Arimidex, Taxmoxifen Alone or in Combination (ATAC), Tamoxifen and Exemestane Adjuvant Multinational (TEAM) and Breast International Group (BIG) 1–98 trials juxtapose cognitive effects of AIs against those of tamoxifen. These and other studies are examined herein to provide a comprehensive overview of the effect of endocrine therapy on cognition.
Third-generation nonsteroidal aromatase inhibitors (AIs), letrozole and anastrozole, are superior to tamoxifen as initial therapy for early breast cancer but have not been directly compared in a head-to-head adjuvant trial. Cumulative evidence suggests that AIs are not equivalent in terms of potency of estrogen suppression and that there may be differences in clinical efficacy. Thus, with no data from head-to-head comparisons of the AIs as adjuvant therapy yet available, the question of whether there are efficacy differences between the AIs remains. To help answer this question, the Femara versus Anastrozole Clinical Evaluation (FACE) is a phase IIIb open-label, randomized, multicenter trial designed to test whether letrozole or anastrozole has superior efficacy as adjuvant treatment of postmenopausal women with hormone receptor (HR)- and lymph node-positive breast cancer. Eligible patients (target accrual, N = 4,000) are randomized to receive either letrozole 2.5 mg or anastrozole 1 mg daily for up to 5 years. The primary objective is to compare disease-free survival at 5 years. Secondary end points include safety, overall survival, time to distant metastases, and time to contralateral breast cancer. The FACE trial will determine whether or not letrozole offers a greater clinical benefit to postmenopausal women with HR+ early breast cancer at increased risk of early recurrence compared with anastrozole.
Anastrozole; Aromatase inhibitors; Breast cancer; Femara; Letrozole; Tamoxifen
For more than 20 years, tamoxifen has been the gold standard for the adjuvant treatment of postmenopausal women with hormone-responsive early breast cancer. However, recent randomized trials have shown efficacy and tolerability benefits with the third-generation aromatase inhibitor anastrozole, resulting in an increased use of this agent in the adjuvant setting. Data on anastrozole’s long-term efficacy and tolerability are therefore of interest in clinical practice and will be reviewed here, especially in the light of the 100-month analysis of the ATAC (Anastrozole, Tamoxifen Alone or in Combination) trial.
anastrozole; aromatase inhibitors; breast cancer; adjuvant therapy
The third-generation aromatase inhibitors (AIs), letrozole, anastrozole and exemestane, are becoming the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen in both adjuvant and metastatic setting. In particular, several large and well designed trials have suggested an important role for AIs in the adjuvant treatment of postmenopausal women with estrogen-receptor positive breast cancer either in the upfront, sequential or extended adjuvant mode. Overall, AIs are associated with a small but significant improvement in disease free survival. The expanding use of AIs in the treatment of early breast cancer means that individual patients will be exposed to the agents for longer durations, making it increasingly important to establish their long-term safety. This review focused on the effects of AIs on bone metabolism, serum lipids and cardiovascular risk. AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures. With respect to tamoxifen AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified. An adequate monitoring of bone mineral density (BMD) and lipid profile could be recommended for post-menopausal women candidate to AIs.
breast cancer; aromatase inhibitors; bone loss; lipids; cardiovascular risk
Breast cancer is one of the leading causes of cancer-related deaths in women. Regardless of prognosis, all women with breast cancer are at risk for early recurrence. Nearly 50% of early recurrences occur within 5 years of surgery, and they peak at 2 years after surgery in women treated with adjuvant tamoxifen. Most early recurrences are distant metastases, which strongly correlate with increased mortality. Treatments that mitigate the risk of early distant metastases (DM) are, therefore, likely to improve overall survival in women with early breast cancer (EBC). Aromatase inhibitors (AIs)—anastrozole, letrozole, and exemestane—have been investigated as alternatives to tamoxifen for adjuvant treatment of hormone receptor-positive (HR+) EBC in postmenopausal women (PMW). AIs are better at minimizing risk of early relapse compared with tamoxifen. However, it is not clear if preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC. The ability to subtype HR+ breast cancer on the basis of biomarkers predictive of response to AIs and tamoxifen would likely be key to determining the most beneficial hormonal treatment within patient subpopulations, but this process requires thorough investigation. Until then, adjuvant therapies that provide the greatest reduction in risk of DM should be considered for all PMW with HR+ EBC. This article reviews the clinical trials of AI adjuvant therapies for hormone-sensitive breast cancer, particularly in the context of how they compare with tamoxifen in minimizing the risk of relapse, occurrence of DM, and breast cancer-related deaths.
Aromatase inhibitors; Distant metastasis; Anastrozole; Letrozole; Exemestane; Tamoxifen
The strategy of using estrogen suppression to treat breast cancer led to the development of aromatase inhibitors, including the third-generation nonsteroidal compounds anastrozole and letrozole, and the steroidal compound exemestane. Aromatase inhibitors potently inhibit aromatase activity and also suppress estrogen levels in plasma and tissue. In clinical studies in postmenopausal women with breast cancer, third-generation aromatase inhibitors were shown superior to tamoxifen for the treatment of metastatic disease. Studies of adjuvant therapy with aromatase inhibitors include (i) head-to-head studies of 5 years of the aromatase inhibitor versus 5 years of tamoxifen monotherapy; (ii) sequential therapy of 2–3 years of tamoxifen followed by an aromatase inhibitor (or the opposite sequence) versus 5 years of tamoxifen monotherapy; (iii) extended therapy with an aromatase inhibitor after 5 years of tamoxifen; and (iv) sequential therapy with an aromatase inhibitor versus aromatase inhibitor monotherapy. Recent results from the Arimidex, Tamoxifen, Alone or in Combination and Breast International Group 1–98 trials advocate using an aromatase inhibitor upfront. This article examines the clinical data with aromatase inhibitors, following a brief summary of their pharmacology.
anastrozole; aromatase inhibitor; breast cancer; estrogen; exemestane; letrozole
Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy.
Patients and Methods
Of 8,010 postmenopausal women with hormone receptor–positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling.
Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months.
Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor–positive breast cancer.
The third-generation aromatase inhibitors (AIs) letrozole, anastrozole, and exemestane are replacing tamoxifen as adjuvant therapy in most postmenopausal women with early breast cancer. Although AIs have demonstrated superior efficacy and better overall safety compared with tamoxifen in randomized controlled trials, they may not provide the cardioprotective effects of tamoxifen, and bone loss may be a concern with their long-term adjuvant use. Patients require regular bone mineral density monitoring, and prophylactic bisphosphonates are being evaluated to determine whether they may protect long-term bone health. AIs decrease the risks of thromboembolic and cerebrovascular events compared with tamoxifen, and the overall rate of cardiovascular events in patients treated with AIs is within the range seen in age-matched, non-breast-cancer populations. AIs are also associated with a lower incidence of endometrial cancer and fewer vaginal bleeding/discharge events than tamoxifen. Compared with tamoxifen, the incidence of hot flashes is lower with anastrozole and letrozole but may be higher with exemestane. Generally, adverse events with AIs are predictable and manageable, whereas tamoxifen may be associated with life-threatening events in a minority of patients. Overall, the benefits of AIs over tamoxifen are achieved without compromising overall quality of life.
Adjuvant therapy; Aromatase inhibitors; Early breast cancer; Letrozole; Safety
Many studies about the adjuvant endocrine therapy of postmenopausal patients with hormone receptor-positive breast cancer have shown significant superiority of aromatase inhibitors (AIs) compared to tamoxifen only. Within these studies, different AIs (anastrozole, letrozole, exemestane) and treatment strategies (upfront, switch, extended adjuvant) were applied.
Material and Methods
The intention of our enquiry was to evaluate the implementation of the results of these studies in German breast cancer centers and university hospitals. Questionnaires were sent to 200 breast cancer centers and university hospitals (returns: 108).
Our enquiry showed that most centers preferred anastrozole as upfront therapy in patients with an intermediate or high risk of relapse. Furthermore, during AI therapy, additional bisphosphonate treatment was applied ‘always’ in only 9% of cases, and in 78% of cases of proved osteopenia/osteoporosis. Surprisingly, 50% of the participating centers do not exclude AIs in premenopausal women.
At the time of our enquiry, anastrozole as upfront therapy was consistent with the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) from 2009. Compared to tamoxifen, AIs increase the risk of osteoporosis, which can, however, be prevented and treated with concomitant bisphosphonate therapy. The rare use of bisphosphonates as well as contraindicated AI therapy in premenopausal patients show amongst others the substantial need for more information.
Breast cancer; Endocrine therapy; Aromatase inhibitors
Following their successful implementation for the treatment of metastatic breast cancer, the ‘third-generation’ aromatase inhibitors (anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancers. These drugs are characterized by potent aromatase inhibition, causing >98% inhibition of estrogen synthesis in vivo. A recent meta-analysis found no difference in anti-tumor efficacy between these three compounds. As of today, aromatase inhibitor monotherapy and sequential treatment using tamoxifen followed by an aromatase inhibitor for a total of 5 years are considered equipotent treatment options. However, current trials are addressing the potential benefit of extending treatment duration beyond 5 years. Regarding side effects, aromatase inhibitors are not found associated with enhanced risk of cardiovascular disease, and enhanced bone loss is prevented by adding bisphosphonates in concert for those at danger of developing osteoporosis. However, arthralgia and carpal tunnel syndrome preclude drug administration among a few patients. While recent findings have questioned the use of aromatase inhibitors among overweight and, in particular, obese patients, this problem seems to focus on premenopausal patients treated with an aromatase inhibitor and an LH-RH analog in concert, questioning the efficacy of LH-RH analogs rather than aromatase inhibitors among overweight patients. Finally, recent findings revealing a benefit from adding the mTOR inhibitor everolimus to endocrine treatment indicate targeted therapy against defined growth factor pathways to be a way forward, by reversing acquired resistance to endocrine therapy.
breast cancer; endocrine therapy; aromatase inhibitors; adjuvant therapy; resistance
The ATAC trial evaluates in a randomized, double-blind design, Arimidex™ (anastrozole) alone or in combination with tamoxifen, relative to tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for ≥3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 ± 4 h after last dose. Trough (Cmin) plasma concentrations of anastrozole, tamoxifen and desmethyltamoxifen (DMT) were measured by validated methods. The PK results were based on a total of 347 patients (131 anastrozole (1 mg o.d.), 111 tamoxifen (20 mg o.d.), 105 anastrozole and tamoxifen (1 and 20 mg o.d. respectively)). The geometric mean steady-state trough plasma concentrations of tamoxifen and DMT were statistically equivalent in patients receiving tamoxifen alone or in combination with anastrozole: geometric mean tamoxifen = 94.8 ng ml−1and 95.3 ng ml−1in tamoxifen alone and combination groups, respectively; geometric mean DMT = 265.1 and 277.6 ng ml−1in the tamoxifen and anastrozole and tamoxifen groups, respectively. The geometric mean anastrozole levels were 27% lower (90% Cl 20–33%;P< 0.001) in the presence of tamoxifen than with anastrozole alone. Baseline plasma oestradiol levels were not obtained in the PK sub-protocol, however, such information was available from a similar ATAC sub-protocol, which evaluated bone mineral density. Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l−1prior to treatment and 3.7, 20.9 and 3.6 pmol l−1after 3 months in the anastrozole, tamoxifen, and combination groups, respectively (n = 167). On-treatment values were below the detection limit (3 pmol l−1) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by tamoxifen is unlikely to be of clinical significance when anastrozole and tamoxifen are administered together. © 2001 Cancer Research Campaign http://www.bjcancer.com
arimidex; tamoxifen; aromatase inhibitor; oestrogen; oestradiol; breast cancer
Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer.
To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting.
From 1998–2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent.
The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization.
Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole.
BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.
There is overwhelming evidence that optimal adjuvant endocrine therapy for hormone sensitive breast cancer in postmenopausal women should include a third generation aromatase inhibitor (AI). On current evidence, adjuvant anstrozole or letrozole should be used upfront in such patients especially in those with high risk disease (node positive and/or tumours > 2 cm). The sequential approach of tamoxifen for 2–3 years followed by exemestane or anastrozole for 2–3 years is a reasonable alternative to 5 years of AI monotherapy in patients with low risk disease (node negative and tumour smaller than 2 cm) especially if the tumour is positive for estrogen and progesterone receptors.
Node-positive patients completing 5 years of adjuvant tamoxifen should be offered letrozole for up 48 months. Further research is required to establish the long-term cardiovascular safety of AIs especially that of letrozole and exmestane, the optimal AI to use, duration of AI therapy and whether monotherapy with an AI for 5 years is superior to sequencing an AI after 2–3 years of tamoxifen.
The bone mineral density (BMD) should be measured at baseline and monitored during therapy in women being treated with AIs. Anti-osteoporosis agents should such as bisphosphonates should be considered in patients at high risk of bone fractures.
Adjuvant tamoxifen therapy substantially decreases the risk of recurrence and mortality in women with hormone (estrogen and/or progesterone) receptor–positive breast cancer. Previous studies have suggested that metabolic conversion of tamoxifen to endoxifen by cytochrome P450 2D6 (CYP2D6) is required for patient benefit from tamoxifen therapy.
Tumor specimens from a subset of postmenopausal patients with hormone receptor–positive early-stage (stages I, II, and IIIA) breast cancer, who were enrolled in the randomized double-blind Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial, were genotyped for variants in CYP2D6 (N = 1203 patients: anastrozole [trade name: Arimidex] group, n = 615 patients; tamoxifen group, n = 588 patients) and UDP-glucuronosyltransferase-2B7 (UGT2B7), whose gene product inactivates endoxifen (N = 1209 patients; anastrozole group, n = 606 patients; tamoxifen group, n = 603 patients). Genotyping was performed using polymerase chain reaction–based TaqMan assays. Based on the genotypes for CYP2D6, patients were classified as poor metabolizer (PM), intermediate metabolizer (IM), or extensive metabolizer (EM) phenotypes. We evaluated the association of CYP2D6 and UGT2B7 genotype with distant recurrence (primary endpoint) and any recurrence (secondary endpoint) by estimating the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox proportional hazards models. All statistical tests were two-sided.
After a median follow-up of 10 years, no statistically significant associations were observed between CYP2D6 genotype and recurrence in tamoxifen-treated patients (PM vs EM: HR for distant recurrence = 1.25, 95% CI = 0.55 to 3.15, P = .64; HR for any recurrence = 0.99, 95% CI = 0.48 to 2.08, P = .99). A near-null association was observed between UGT2B7 genotype and recurrence in tamoxifen-treated patients. No associations were observed between CYP2D6 and UGT2B7 genotypes and recurrence in anastrozole-treated patients.
The results do not support the hypothesis that CYP2D6 genotype predicts clinical benefit of adjuvant tamoxifen treatment among postmenopausal breast cancer patients.
Introduction: Tamoxifen is associated with a twofold increased risk of thromboembolic events. Third generation aromatase inhibitors (AIs), such as letrozole, anastrozole, and exemestane have therefore replaced tamoxifen in the adjuvant therapy of hormone receptor-positive breast cancer. A retrospective review was performed in patients who underwent delayed microvascular breast reconstruction and received tamoxifen at the time of surgery in order to assess the risk of both minor and major flap complications including thromboembolic events.
Patients and methods: Twenty-nine patients who underwent delayed microsurgical breast reconstruction with autologous tissue between 2006 and 2012 were included in the study. The overall complication rates were compared between patients who did versus those who did not receive tamoxifen at the time of microsurgical breast reconstruction.
Results: Breast reconstruction was performed with a DIEP flap in 25 patients and with a TRAM flap in 4 patients. Overall, the complication rate was 37.9% (n=11) consisting of 5 major (including one total flap loss) and 6 minor complications. In patients receiving tamoxifen (n=5), we observed one minor complication and one major complication with a total flap loss due to thrombus formation at the anastomosis site. In one patient pulmonary embolism occurred without association to tamoxifen. The number of thromboembolic events was equivalent in both groups (p=0.642). No increase of major (p=0.858) or minor (p=0.967) complications in the tamoxifen group could be observed. Taking the overall complication rate into account there was no statistically difference between the two groups (p=0.917).
Conclusion: In our study we could not observe an increased risk for thromobembolic events in patients receiving tamoxifen while undergoing autologous microvascular breast reconstruction.
Tamoxifen; breast cancer; adjuvant therapy; microvascular breast reconstruction
Anastrozole is the first aromatase inhibitor to show a significant survival advantage over megestrol acetate in post-menopausal women with advanced breast cancer. The rationale for extending the use of aromatase inhibitors to the treatment of early breast cancer is based on the efficacy observed in the advanced setting, combined with good tolerability and a convenient dosing regimen. Furthermore, oestrogen deprivation by ovarian ablation (similar to oestrogen antagonism with tamoxifen) is already established as an effective adjuvant treatment in premenopausal women with modality breast cancer. Anastrozole produces a profound suppression of plasma oestrogen levels which is greater than that obtained with earlier aromatase inhibitors (formestane, aminoglutethimide) or megestrol acetate. This could account for the differences in clinical efficacy seen between anastrozole and megestrol acetate. In terms of benefits over other endocrine agents, anastrozole causes significantly less weight gain than megestrol acetate; it does not have the partial agonist activity of tamoxifen, and is unlikely to lead to tumour stimulation in patients resistant to tamoxifen or to exert proliferative effects on the endometrium. The lack of oestrogen agonist activity, however, may possibly have detrimental effects on bone mineral density and blood lipid profile. Current clinical trials are investigating the efficacy and safety of anastrozole in the early breast cancer setting. The results of these trials will help to determine whether anastrozole has any benefits over tamoxifen, the current treatment of choice in post-menopausal women with early breast cancer.
Gene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen.
To clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. The CCND1 amplification status and protein expression of cyclin D1 were assessed by chromogenic in situ hybridisation and immunohistochemistry, respectively, in 1,155 postmenopausal, oestrogen-receptor-positive breast cancer patients included in the TransATAC substudy.
Amplification of CCND1 was observed in 8.7% of the tumours and was associated with increased risk of disease recurrence (hazard ratio = 1.61; 95% confidence interval, 1.08 to 2.41) after adjustment for other clinicopathological parameters. In contrast, nuclear expression of cyclin D1 protein was associated with decreased recurrence rate (hazard ratio = 0.6; 95% confidence interval, 0.39 to 0.92). The intensity of nuclear or cytoplasmic expression was not of prognostic value. There was no significant interaction between cyclin D1 status and treatment efficacy, ruling out any major detrimental effect of tamoxifen in CCND1-amplified postmenopausal breast cancer.
In summary, CCND1 amplification and low nuclear expression of cyclin D1 predicted poor clinical outcome in postmenopausal breast cancer patients treated with either anastrozole or tamoxifen.
Current Controlled Trials ISRCTN18233230.
The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor–positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment–related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score < −2.5) and considered on an individual basis for those with osteopenia (T score < −1). Modifiable lifestyle behaviors including adequate calcium and vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor–positive breast cancer.
The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone.
In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor–positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women.
At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy.
Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)
Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant A) 5-years tamoxifen, B) 5-years letrozole, C) 2-years tamoxifen followed by 3-years letrozole, or D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) versus tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores =0.28, p=0.04, 95% CI:0.02, 0.54, Cohen's D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen.
Cognitive function; breast cancer; aromatase inhibitor; tamoxifen; letrozole; quality of life

domain: biology


text:
Neurobiological Narratives: Experiences of Mood Disorder Through the Lens of Neuroimaging, by Daniel Buchman
In Canada, adults diagnosed with major depression or bipolar disorder were asked their ideas about the potential role of neuroimages in stigma mitigation, moral explanations of mental illnesses, and the legitimation of psychiatric symptoms. The resulting interviews show the complex and ambivalent ways in which individuals integrate brain-based notions of mental disorders into their self-understanding; some assumed neurobiological explanations of their disorder yet struggled against pharmaceutical treatments (Buchman et al. 2013).
Vidal, Fernando and Ortega, Francisco. Being Brains: Making the Cerebral Subject (Forms of Living) (...
You can request he full text of Gilbert's article at researchgate.net
You can download the full-text article at the link below:Buchman Daniel Z., et al. 2013. “Neurobiological Narratives: Experiences of Mood Disorder Through th...Obtained from:
utoronto.academia.edu/DanielZBuchmanTake a look at his twitter too!
Sign in or create a free account

domain: library


text:
View from Davis Bay, BC looking over to Vancouver Island
Great Blue Heron (Ardea herodias)
Location: Lynn Canyon Park, North Vancouver, British Columbia, Canada
Young Girl with a Great Blue Heron
Storm over Georgia Strait taken from the Sechelt Boulevard
Kayaking in Hotham Sound, British Columbia. I really like the variety of natural colours in the rock and the purple wildflowers are the icing on the cake.

domain: geography


text:
New Study on Immunotherapy
San Francisco, California- [January 25, 2018] - The Cancer Support Community (CSC) announced today at the 2018 ASCO-SITC (American Society of Clinical Oncology-Society of Immunotherapy of Cancer) Clinical Immuno-Oncology Symposium the results of its survey analysis assessing the needs of immunotherapy patients, caregivers, and health care providers.
The survey’s release comes on the heels of a Washington Post story earlier this month examining patient reactions to immunotherapy treatments. The CSC survey, which was conducted in early 2017, sought to better understand and identify key areas of concern or gaps in knowledge and patient care related to immunotherapy as identified by patients, caregivers, and health care providers.
“The findings highlight the need for easily accessible and comprehensive information on immunotherapy,” said Linda House, CSC president. “The Cancer Support Community is committed to providing this solution through our innovative Immunotherapy & Me program that supports the unique needs of patients receiving immunotherapy treatment and the clinical staff who care for them.”
The CSC materials will be an important tool for the patients, caregivers, and providers who revealed the following experiences in the study:
- Most patients (52.4 percent), and nearly 40 percent (39.3 percent) of caregivers, reported that understanding how immunotherapy works and managing treatment-related side effects were ‘quite a bit’ or ‘very much’ of a problem during immunotherapy treatment.
- Among health care providers, about 40 percent indicated that understanding how immunotherapy works and managing treatment-related symptoms and side effects are ‘quite a bit’ challenging for their patients; nearly half (48.7 percent) also stated that finding support with issues related to cancer care was also ‘quite a bit’ challenging for their patients.
- 60 percent of caregivers and nearly 45 percent (44 percent) of patients stated that an online tool/website to manage their immunotherapy (IO) treatment would be ‘quite a bit’ or ‘very much’ helpful to them.
- Nearly 30 percent (29.8 percent) of patients and 50 percent (48.2 percent) of caregivers reported that they would be willing to use an online tool to help manage their, or their loved ones, immunotherapy treatment on a ‘weekly’ basis.
- Of note, almost 90 percent (86 percent) of health care providers reported that they were ‘quite a bit’ or ‘very much’ likely to refer patients to immunotherapy and cancer-related print materials. Well over half (59.3 percent) stated that they were ‘quite a bit’ or ‘very much’ likely to refer their patients to an online tool to help manage their immunotherapy treatment.
House shared the findings at 2018 ASCO-SITC Clinical Immuno-Oncology Symposium. The full poster as presented at the Symposium is available online. The CSC website includes additional information about the Immunotherapy & Me pilot program.

domain: medical


text:
Nic Armstrong & The Thieves
The Greatest White Liar
e didn’t really hit it off, this CD and I. Imagine us, if you will, at a cheesily clichéd restaurant date setting—ignore the obvious impracticalities of turning menu pages with a hard plastic exterior, that’s my problem and I’m dealing with it—instead ponder the resultant meaningless small-talk between two people who quickly realise they will probably never see one another again. Sure, the experience (or the food, at least) may have been bearable enough, but there’s simply no desire for a repeat. This presents something of a difficulty in the reviewing stakes. Or, indeed, the reviewing of steaks.
You presumably want to know what this record is like. I want to tell you—really, I do. But I want to do it in such a way that concurrently justifies the existence of this momentary collection of paragraphs in the first place. Which means this will have to be a self-indulgent concept-review. You lucky people.
Except I couldn’t settle on a single idea. So, just as the most interesting works at artistic exhibitions are always delicate fragments of sketchbooks and notepads detailing the painstaking working process behind a finished piece, I hope the upcoming exploration of my own thought processes will provide a curiously short-lived thrill. Probably followed by a period of confusion and anger. A bit like the one you might get when spying a long-anticipated parcel arriving in the mail only to discover that it is, in fact, a box of wasps.
1) “The Political Satire”
This was my initial, crushingly terrible, idea. Based on the most tenuous premise (the appearance of the word ‘liar’), I planned to pen a deliciously clever comparison between the derivative 60s homage of The Greatest White Liar and the perjury-tastic antics of ex Tory Party Deputy Chairman, Jeffrey Archer. This quickly collapsed, as the only link I could conjure up involved this album and Archer’s books both being rather bland and owing a large debt of thanks to other sources (The Stones/The Kinks and Mrs Archer’s creative writing abilities, respectively). Not quite the devastating attack that the gimp-faced weasel of British politics deserves.
2) “The Secretly Writing About Something Else In Disguise”
Churning out fabulous insights into records lacking in personality is a thankless task. Much better, then, to just spill the contents of your heart and pretend they somehow relate to the object under discussion. I had an elaborate plan to compare various aspects of this recording to classic moments from 48k Spectrum gaming. Instead of referring to the Stereophonics when attempting to convey some of Nic Armstrong’s more dubious attempts at an authentic rock grrrrowl, I would explain that it sounds a little bit like the poorly sampled cry of “Fantasy World Dizzy!” which opens the game of the same title—ie; a gruff old man with a larynx consisting of 90% phlegm. This concept chewed itself up like a overused cassette when I realised that a dodgy metaphor involving Horace Goes Skiing would (thankfully) be lost on nearly every single person in the known world.
3) “The Not As Clever As It Thinks It Is”
In which I would stretch my meagre attempts at creating a thematic review into a whole piece *about* stretching my meagre attempts at creating a thematic review and, by extension, the entire concept of a concept-review. Everyone reading would subsequently drown in a mighty ocean of self-referential horror and forget that I hadn’t talked about Nic Armstrong & The Thieves very much at all. Which is what happened. Or WAS it?
I can tell you’re feeling a bit cheated. Sorry about that. Let me make it up to you by offering a chance to win my copy of this record. Yes! You could soon be the proud owner of this unassumingly fuzz-guitared, gently blues-ey and sometimes arpeggio-riffic nostalgia flashback. I have no further use for it—but it’s possible that you may wish to treasure it. If your town has banned all works produced by British guitar bands between 1965 and 1969, or something.
Simply email my Stylus staff address with the heading “your review was frightfully pretentious and I demand my compensation” and a plausible reason for me to expend postage costs on your insatiable greed. The best reason, decided by myself on a whim, will win the album. At which point I’ll need your address, so don’t bother entering if you think I might use this information for evil and dubious purposes. Such as sending you a box of wasps.
You must also answer this insultingly easy question:
One of these people is not famous for their thieving; but who?
a) Garrett, from the superbly excellent PC game Thief.
b) Robin Hood, notorious English thief.
c) Ronnie Biggs, Britain's most notorious fugitive.
d) Dr. Egon Spengler.
Good luck, readers!
Reviewed by: Peter Parrish
Reviewed on: 2005-07-29

domain: artistic


text:
Across the globe, more nuclear power units are under construction today than at any other time in the last 25 years. This is happening despite the 2011 crisis in Japan at Fukushima. It is important to note the Fukushima crisis and resulting problems was not a result of a nuclear disaster, but rather a tsunami that laid waste to large parts of Japan and killed around 20,000 people.
At the start of 2015 there were 436 operating nuclear reactors across the globe. By year-end this had increased to 439, despite the closure of seven units during the year. The countries driving nuclear construction are largely in Asia, with China, at last count, building 30 new reactors to add to their fleet.
In South Africa, it’s clear that the government is intent on pressing ahead with a new nuclear build program. The Integrated Resource Plan calls for 9,600MW of nuclear power and this still seems to be the target for the new build. One reason seemingly being that since nuclear is an expensive and complicated industry; it would simply be more cost effective over the long term to invest in a fleet of reactors that can be supported by an underlying industry. If this should transpire, it will certainly lead to a boom in jobs across many sectors of industry.
The environment is another reason nuclear power is punted as an option for South Africa. At the United Nations Climate Change Conference in December, countries reached an agreement to hold the average global temperature increases to less than 2 degrees Celsius, compared to preindustrial levels. The targets agreed upon will require significant reductions in the global greenhouse gas emissions and one of the major areas targeted for reduction of carbon dioxide outputs would be energy generation. The bulk of the globe’s electricity is still generated by fossil fuels, with nuclear power supplying roughly 10% of global electricity. The use of nuclear power is recognized as being a means to achieve climate change targets.
Another serious question around South Africa’s energy future is the planned decommissioning of old power plants. By 2030, Eskom, by law, must close down 14,800MW of existing capacity, while Eskom’s new mega build projects will only add 10,932MW over the same period. These older plants are currently supplying a large part of South Africa’s baseload electricity. The country can ill afford to lose such a big part of its capacity and there is still no clear plan as to what will replace this baseload capacity. The role of renewables is limited; the availability of power output from renewable energy is still not comparable to that of fossil fuel or nuclear plants. Add into the mix the environmental considerations and there is only one option to replace old baseload with new baseload – nuclear.
The major constraint to a new nuclear build in South Africa is funding. Accurate estimates of what a 9,600MW fleet could cost are largely unavailable; they range between $45.4 billion and $68 billion. The only thing we know for sure is that is going to be very expensive. There are other concerns over safety, waste and the ability to run a corruption free and timeous build process.
However, there are also some benefits. The country cannot ignore the environmental issues and the need for a reliable baseload power system that can allow the economy to grow. The South African economy may be moving away from mining but there is no need to ignore the potential in the future of mining, as well as in added beneficiation. Reaching this potential would require a lot of electricity and of course, the more the economy grows, the greater the need for electricity.
Where will the first new plant be built? The Eastern Cape province still seems the most likely area. When will the first new reactor be built? The current economic downturn has given the country some breathing room and the pressure is off for now, but there can be little doubt that new construction could start within the next two years. Following that, the full fleet of 9,600MW could follow over the following 20 years. In addition, given government’s appetite for nuclear power, I would not be surprised if South Africa sees more than 9,600MW of nuclear power by 2050.
Is that a good thing? Time will tell.
James-Brent Styan authored a book on the energy crisis called Blackout, The Eskom Crisis. It was published in 2015. He writes in his personal capacity.

domain: news


text:
KENYA: TWO SENTENCED TO DEATH FOR ROBBERY WITH VIOLENCE
May 4, 2015: Two men were sentenced to death by hanging in Kenya after being found guilty of murder and robbery with violence. Francis Githinji Gachogu, 38 and Stephen Githinji, 35, were charged with the murder of Samuel Kigotho who was a watchman at Gikindu Primary School in Kimacharia, Mathioya. The death sentences were issued by a court in Murangâa.
They carried out the offences at the school on February 7, 2011.
The body of the night guard was discovered by school children. Giving the judgment, Chief Magistrate Bildad Ochieng said the offences were cruel and heartless. (Sources: The STAR, People Daily, 4th May, 2015)

domain: sociology


News in from 2016 graduate Hollie Crawshaw.
“My Country Shows Of Gloucestershire series has been featured in the latest issue of The Countryman as a five page photo essay! The publication is a popular rural magazine and is another aspect of promotion for my photo book, which was released at the beginning of June. I am currently doing a lot of promotion for the book which includes attending many shows. I am also doing a book signing at this years Autumn Malvern Show at the Three Counties Show ground on Sunday 24th September.
News in from 2017 graduate Katie Mordan.
“I am delighted and honoured to have been shortlisted for the 2017 South West Graduate Photography prize having entered with a selection of images from my series Planted. Eight finalists have been chosen and our work will be in exhibition at PHOTOBLOCK 2017, Old Truman Brewery, London, later in the year and one overall winner will then be chosen by industry professionals to win a paid commission.
This competition has been running since 2010 and graduates from photography courses in the south west are invited to enter. It’s one of the few free to enter competitions, so I highly recommend all the new third years entering the 2018 competition next year.”
This in from second year Ellie Ramsden.
“I’ve been working with songwriter, Carla Marie Williams, for the past couple of weeks. Carla has written songs for Beyonce, Britney Spears and Girls Aloud, and is currently working on a project to help improve the level of gender equality within the music industry. I’ve been creating images and filming Carla for her personal use and for #GirlsIRate in the recording studio, at the BBC and at the #GirlsIRate Summer Soiree.
Some of the work can be seen on my Instagram account here: https://www.instagram.com/carlamarieuk/
This just in from 2017 graduate Erin McGurk.
“I have recently been in contact with a local secondary school and sixth form about the issues surrounding social media and the way it can affect the mental health of students. I showed them my film – created as part of my FMP – and they were eager to work with me . As a result they want me to host an evening for parents and invite local organisations to show them the film and lead a presentation on research around the subject which I feel well prepared for having done a lot research into the topic for my Final Major Project”.
“Having spoken with the Head of Support at the school, my passion and drive to publicise this matter has heightened as more and more people are talking and noticing this problem but there’s a lack of guidance of how to tackle the issue”.
T”his is a positive step the right direction for me and I am keen to see how it develops. I am pleased that my film is having the desired impact on a wider audience and allowing me to create a conversation from the issues it address’s”.
It has just been a few weeks since our third year students handed in their final work for marking but they are all ready securing themselves exciting jobs and work experience.
We just received this email from 2017 graduate Katy Layton.
“A few weeks ago, I went for an interview for the position (over 150 people applied for the role) of editorial and digital assistant at Homes & Antiques magazine. As a result, I was offered the position and I have just completed my first full week in my new job. I am loving every moment of working with the magazine and alongside the fantastic team. I am constantly learning something new and I am looking forward to seeing where this opportunity can take me in the future. I have taken the first step into my dream career and it all started from completing a work experience with the magazine as part of the professional practice module in my second year!”
We would also like to congratulate Holly Davis on securing a post-production role within the Superdry team in Cheltenham, Shannon Dudley on securing a production role within a company in Oxford, Carly Tyrell who is currently on a European Tour with US band Linkin Park and Reece Pickering who assisted the photographer Gavin Bond photographing Liam Gallagher last week.
We will keep you informed of all the 2017 graduates success over the coming weeks.
Above: Personal work created by second year Alex Duffill.
“These images were created on a commission with the British team Neon Velo, at the Beaumont Trophy race in Stamfordham, Northumberland. I was documenting the team throughout the two days of the race preparation, the race itself and then after the race had been completed”.
Each year first and second year students studying in universities across England are questioned as to how satisfied they are with the course they are studying on. These are known as the ACE results and are released at this time each year. We are proud, pleased and excited to announce that this year we have received a score of 100% satisfaction from our students.
A big thank you to all of the students who responded to the survey and to the lecturers who help to make the course what it is!
Above: A dramatic image of the work currently being exhibited by our third year’s (Level 6) as part of their final degree show exhibition within our Hardwick Campus in Cheltenham, Gloucestershire. Image: Erin McGurk.
Just in from second year Laura Barnett.
“Since working with MONU Skin Professional Skincare in a work experience capacity as part of the Professional Practice module they have offered me a part-time position to help run their social media channels and take main control of their Instagram. This involves me creating monthly plans and content including stills, stop motion and moving image. I will also be working to find brand ambassadors through social media for the company along with creating an ambassador programme”.


Feb. 7, 2012
WHAT: Bucknell (18-6, 8-0 PL) at Colgate (7-16, 1-7 PL)
WHERE: Cotterell Court, Hamilton, N.Y.
WHEN: Wednesday, Feb. 8, 7 p.m. ET
LIVE WEBCAST: Bison Vision
RADIO: Eagle 107 (WEGH 107.3 FM) and SportsJuice.com
LIVE STATS: GoColgateRaiders.com
Complete Game Notes in PDF Format
With a Win over Colgate, Bucknell Would ...
• ... win its 11th straight game and improve to 19-6 on the season.
• ... establish the team’s longest winning streak under coach Dave Paulsen.
• ... sweep the season series against the Raiders.
• ... get out to an 9-0 start in Patriot League play for the second time ever (2006).
• ... maintain a two-game lead in the Patriot League standings.
• ... win its 19th straight game against Patriot League foes dating back to last season (including postseason), extending the longest conference winning streak in the nation.
• ... win its seventh straight road game and improve to 9-5 on the road this season.
• The red-hot Bison hit the road Wednesday night to take on Colgate at Cotterell Court. Winners of 10 straight games overall, Bucknell is 8-0 in the Patriot League and holds a two-game lead over American and Lehigh with six games remaining. Colgate enters the game in seventh place at 1-7.
• Bucknell has won 10 straight games, 13 of its last 15, and 18 of its last 22. Since Dec. 1, 2010, Bucknell is 41-9.
• Bucknell’s current 18-game winning streak against conference opponents is the longest in the nation. The Bison’s last Patriot League loss came at the hands of Army, 90-70 at West Point on Jan. 29, 2011.
• Last time out, Bucknell pulled away late for an 81-68 home victory over Army on Saturday night. Colgate is coming off a tough 59-58 home loss to American in which a potential game-winning shot rimmed out in the final seconds.
• Mike Muscala is averaging 19.3 points over his last 14 games, and he has upped his season scoring average to 16.3, fourth-best in the Patriot League. Cameron Ayers (11.5), Joe Willman (10.1) and Bryson Johnson (9.5) are also top scorers.
• Muscala continues to lead the Bison in rebounding (9.3) and blocked shots (1.5). He leads the Patriot League in rebounding by a wide margin, and he has 11 double-doubles this season, the most in the league. He is five shy of the school record for double-doubles in a season.
• Bryan Cohen has also been red hot of late. Cohen scored a season-high 19 points in Saturday’s win over Army, and the senior guard is averaging 10.0 points per game while shooting 57.4% from the floor and 69.2% from 3-point range in Patriot League play.
• The Bison were unanimously picked as the preseason favorite in the Patriot League by the league’s head coaches and SIDs.
• The Bison returned four starters from last year’s team that finished 25-9 overall and 13-1 in the Patriot League. Bucknell went on to capture the Patriot League Tournament title, but the 14th-seeded Bison were ousted by red-hot Connecticut, the eventual national champions, in their NCAA Tournament opener.
How to Get the Game
• The Bucknell-Colgate game will not be televised, however a live webcast will be available on Bison Vision via BucknellBison.com as well as Patriot League All-Access via PatriotLeague.com (subscription rates apply).
• The game can be heard in the Susquehanna Valley on the radio on Eagle 107 (WEGH 107.3 FM), with Doug Birdsong and Terry Conrad describing the action. The pregame show begins 30 minutes before tip-off.
• The audio feed is available online free of charge via BucknellBison.com and SportsJuice.com.
• Live statistics are available at GoColgateRaiders.com.
Television Added for Lafayette Game
• Saturday's Bucknell-Lafayette game at Sojka Pavilion will now be televised on ESPN3 and ESPN Full-Court, in addition to RCN cable systems around the country and WBPH-60 in Eastern Pennsylvania.
Patriot League Success
• The Bison are 196-92 (.681) in Patriot League regular-season games, the best record of any league team. Including this season, they have finished at least .500 in PL play in 18 of 22 seasons.
• The victory at Lehigh on Jan. 18 made Bucknell the first Patriot League team to go 100 games over .500 in league play.
• The Bison won a league-record 23 straight contests against conference foes from Feb. 23, 2005 to Jan. 12, 2007.
• Bucknell had a streak of 35 straight wins at home against conference opponents come to an end in 2008. The Bison have currently won 13 in a row at home against league foes.
• Bucknell is one of eight Division I programs still unbeaten in its league (through Monday’s games).
• Bucknell has won 18 straight games against Patriot League foes, 15 in the regular season and three in the Patriot League Tournament. Bucknell owns the longest active conference winning streak (including postseason) among Division I teams.
NCAA Leaders, Consecutive Wins vs. Conference Opponents (through Monday’s games)
Streak Team (Conference) Next Game
18 Bucknell (Patriot) Feb. 8 at Colgate
15 Kentucky (SEC) Feb. 7 vs. Florida
11 Mississippi Valley State (SWAC) Feb. 11 at Alcorn State
11 Murray State (Ohio Valley) Feb. 9 vs. Tennessee State
11 Saint Mary’s (West Coast) Feb. 9 at Gonzaga
Bucknell vs. Colgate
• This will be the 98th all-time meeting between Bucknell and Colgate in a series that dates back to 1920. The Bison have a 57-40 series lead.
• As Patriot League rivals, Bucknell has won 36 of the 49 meetings, including 19 of 22 in Lewisburg.
• Bucknell is 9-1 against Colgate at Sojka Pavilion. The Raiders won there in the arena’s inaugural season (2002-03), but since then the Bison have won nine in a row, including a 70-57 verdict back on Jan. 11.
• Bucknell is 10-4 in its last 14 games in Hamilton.
• Bucknell has won five straight over Colgate, sweeping the season series in each of the last two seasons. Last year, Bucknell won 76-49 at home and 77-69 at Cotterell Court.
• In the first meeting this season at Sojka Pavilion, Bryson Johnson scored 17 points and Mike Muscala added 13 points and 11 rebounds to lead Bucknell to a 70-57 victory. Bryan Cohen scored 11 of his 13 points in the second half, as the Bison maintained a lead of at least eight points for the game’s final 22 minutes. Brandon James and Pat Moore scored 10 points each to lead Colgate.
Last Time Out
• After being honored prior to the game for scoring his 1,000th career point, Bryan Cohen went out and added 19 more to his total to lead Bucknell to a hard-fought 81-68 win over Army on Saturday night at Sojka Pavilion. Cohen went 8-for-10 from the floor and helped break open a close game in the second half with three drives to the basket, two of which resulted in 3-point plays.
• Mike Muscala had another big game with 16 points, while Bryson Johnson added 14 and Cameron Ayers 12. Johnson made his first four 3-point attempts of the night before finishing 4-for-5. Ayers scored 11 of his 12 points in the second half, including one stretch late in the game when he scored on three straight possessions after having a tooth knocked out in a hard collision along the sideline.
• Bucknell shot 70.8% from the floor in the first half en route to a 42-34 lead. Ayers went 0-for-5 in the first half, but the rest of the team was 17-for-19. The Bison finished at 61.4% for the game, equaling their season best (Binghamton).
• The game was tied three different times in the second half, but Cohen’s 3-point play with 10:49 remaining gave the Bison the lead for good.
• Bucknell finished with a 26-21 rebounding edge and forced 14 turnovers.
• Cohen was also sharp defensively, as he helped limit the Patriot League’s third-leading scorer, Ella Ellis, to 13 points on 4-for-10 shooting from the field.
Stats Worth Noting
• Bucknell is now 10-0 since point guard Ryan Hill joined the starting lineup.
• The Bison are 14-0 when leading at the half.
• Bucknell has shot 50% or better as a team in nine of its last 15 games. The Bison have shot 50% 11 times this season and are 11-0 in those games. Bucknell ranks 7th nationally in 3FG% at 40.9%.
• In the last nine games, Bucknell is shooting 47.1% (56-119) from 3-point distance.
• Bucknell leads the Patriot League in both field goal percentage (.472) and field goal percentage defense (.396).
• During this current 10-game winning streak, Bison opponents are shooting 37.1% (194-523). Only three of those 10 teams (Dartmouth, Lafayette, Army) have eclipsed 40%.
• The Bison rank 36th nationally (out of 338 teams) in fewest turnovers per game (11.9), but they only rank 266th in turnover margin (-1.7). Bucknell averages only 4.0 steals per game (335th), but it has counterbalanced that with a good FG% defense and strong defensive rebounding.
• Bucknell has been dominant on the glass for most of the year. After going -15 in rebound margin against Minnesota and Vanderbilt to start the season, the Bison are +157 since then and have outrebounded every opponent except Syracuse, Loyola, Lehigh and American. Bucknell’s +6.0 rebound margin for the season is by far the best in the Patriot League and ranks 28th nationally.
• A big part of Bucknell’s rebounding success has been limiting opponents’ second chances. The Bison have held 17 of their 24 foes to eight or fewer offensive rebounds.
• Bucknell has been better at the free-throw line of late. After shooting just 68.5% at the line in their first 10 games, the Bison have made 79.2% (228-288) as a team in the last 14 contests. That includes a 21-for-21 performance in the win over Richmond, 15-for-15 in the win at Lafayette, and 10-for-10 in the win at Navy. Bucknell ranked third in the nation in free-throw shooting last season at 78.8%, and after the slow start the team is up to 75.1% this season.
• If you remove the freshman class from the free-throw ledger, Bucknell would be shooting 79.5% as a team, which would rank second in the nation, just five percentage points behind Weber State.
• Strangely, Bucknell has been a much better free-throw shooting team on the road this season. The Bison shoot 78.9% as a team in road games, but only 71.3% at Sojka Pavilion.
• Eight Bison have had at least one double-digit scoring game this season, and 10 of the 14 on the roster have done it at least once in his career.
Let’s go Streaking
• Bucknell’s early five-game winning streak was its longest in the months of November or December since the 2005-06 team started the season 5-0.
• The only longer November/December winning streaks in program history were a six-game streak in 1983-84 and a seven-gamer in 1956-57.
• Bucknell had its 18-game home-court winning streak snapped by Loyola on Dec. 28. The record remains a 24-game streak set across the 1985-86, 1986-87 and 1987-88 seasons.
• The 18-game home winning streak was the 11th-longest in the nation when it was broken.
• Bucknell’s current 10-game winning streak is tied for seventh-longest nationally. Murray State’s 23-game streak is No. 1.
• The last streak of longer duration than this current 10-game streak came in 2006-07, when the Bison set a modern-day record with a 14-game win streak.
• The 10-game winning streak is tied for 11th-longest in program history.
Longest Winning Streaks in Bucknell History (broken up by):
17* 3/1/1902 - 2/19/1904 (Allegheny)
15* 2/5/1901 - 2/11/1902 (at Princeton)
14 1/17/2007 - 3/4/07 (at Holy Cross, PL championship game)
14* 1/10/1908 - 1/27/1909 (at State College)
13* 3/9/1906 - 3/9/1907 (at Harrisburg Collegians)
13* 2/15/1918 - 2/8/1919 (at Lehigh)
12 1/7/2006 - 2/18/2006 (at Northern Iowa)
11 12/4/2004 - 1/23/2005 (at American)
11 2/1/1993 - 3/6/1993 (Holy Cross, PL championship game)
11* 2/6/1920 - 1/13/1921 (at Temple)
10 12/31/2011 - present
10 2/5/2011 - 3/17/11 (Connecticut, NCAA Tournament)
10 1/14/1984 - 2/8/1984 (at Lafayette)
10* 2/16/1919 - 12/20/1919 (at Syracuse)
9 12/28/2010 - 1/29/2011 (at Army)
9 1/21/1987 - 2/21/1987 (at Lafayette)
9 1/7/1975 - 1/25/1975 (Rutgers)
9* 2/19/1959 - 12/10/1959 (at Cornell)
9* 3/3/1956 - 12/28/1956 (vs. West Virginia Tech)
8 1/13/1996 - 2/7/1996 (at St. Bonaventure)
8 1/6/1989 - 1/25/1989 (at Delaware)
8* 2/26/1909 - 1/31/1910 (Allegheny)
* Streak carried over multiple seasons
Longest Active Division I Winning Streaks
Streak Team Next Game
23 Murray State Feb. 9 vs. Tennessee State
15 Kentucky Feb. 7 vs. Florida
13 Texas-Arlington Feb. 8 at Sam Houston State
12 Saint Mary’s Feb. 9 at Gonzaga
11 Drexel Feb. 8 at James Madison
11 Mississippi Valley State Feb. 11 at Alcorn State
10 BUCKNELL Feb. 8 at Colgate
10 Long Beach State Feb. 9 at Pacific
9 VCU Feb. 8 vs. Towson
• After the Colgate game the Bison return home to face Lafayette on Saturday at 7 p.m. at Sojka Pavilion.
• The Bison defeated the Leopards 79-65 in Easton on Jan. 14.


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SINGAPORE - Prime Minister Lee Hsien Loong on Wednesday evening kicked off two exercises to distribute items that will help people here to better cope with the haze.
As guest-of-honour at the COMNET@ Teck Ghee Senior Activity Centre in Ang Mo Kio, he distributed sets of masks to about 100 seniors at the centre.
The AIR+ Smart Masks, which can be fitted with a micro ventilator that helps with air ventilation, are innovations of homegrown engineering company ST Engineering.
The seniors, all aged above 60, were guided on the correct way to wear the mask, which can filter harmful PM2.5 pollutant particles from the air.
About 29,000 masks and 6,000 micro ventilators will be distributed at the 60 senior activity centres across Singapore by the weekend.
This is a $300,000 initiative of Temasek Cares and ST Engineering.
Mr Richard Magnus, chairman of Temasek Cares, said: "The haze is at unhealthy levels. Our senior citizens are especially vulnerable. These locally-designed masks and ventilators will help them."
At the event Mr Lee also kickstarted the nationwide distribution of the People's Association (PA) WeCare PAcks, each of which has one N95 mask, instant noodles and beverages, canned food and Vitamin C tablets.
The items were donated by FairPrice Foundation and the local business community.
In all, about 30,000 vulnerable households comprising seniors, and residents with medical conditions who are living alone, will benefit from the distribution.
PA chief executive director Ang Hak Seng said the packs will help seniors, especially those suffering from respiratory difficulties, by reducing the need to venture out to buy food in the haze. The distribution of the WeCare PAcks is expected to be completed within a week, with the bulk of the households receiving them by this weekend, he added.


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MAILEEN DUMELOD HAMTO Reviews
PAGPAG: The Dictator's Aftermath in the Diaspora by Eileen R. Tabios
(Paloma Press, San Mateo, 2020)
It’s an unfortunate and ugly reality that many people in the homeland are so destitute, so poor, that they make a necessary living out of garbage. The practice of “pagpag” involves going through mountains of trash to salvage food and anything else than can be saved to be resold, reused, or traded for other goods. Eileen Tabios’ explains that her latest short story collection, PAGPAG, is so named to shed light on the ever-increasing economic inequities among the urban poor in the Philippines, casualties of decades-long theft, graft and corruption among elected officials and their cronies.
The stories in PAGPAG offer insights to the process of reconstituting a salvaged and made-new life after expulsion, making the most out of the refuse of life in the diaspora. In the book’s introduction, Tabios specifically calls out the Marcos dictatorship for the harms caused to Filipinos who fled the country to escape the violence and turmoil of the Martial Law era (1972-1986), as well as the torment endured by millions of Filipinos who had little choice but stay behind. The author was a child when her family escaped the talons of martial law under the Marcos regime. She draws a link between the damages wrought by the Marcos regime to the renewed clamor for strongman-style leadership that led to the election of Rodrigo Duterte in 2016. The dictator not only ransacked the treasury, he also drove away the collective memory about the painful truths of those difficult and repressive years.
Reading the stories of PAGPAG was a cathartic experience: I was born under Martial Law, and was in elementary school when the first “People Power” toppled the Marcos regime in 1986. My family was among the urban poor in Manila’s working-class section of Sampaloc. I personally observed my parents struggle through finding and keeping jobs. I experienced the ineptitude of government in providing basic needs, such as access to potable water and electricity. Brownouts and water shortages were all-too-common. Criticisms of the government were often shared in hushed tones; one can never be certain about whose ears are listening.
PAGPAG's stories are important in countering the infuriating and disheartening trend of revisionist history of the Marcos legacy among millennials in the homeland. The author reminds us of a time when the Philippines was the shining star of Asia, when Filipinos and the rest of the world believed that the Philippines would soon rival Japan in economic production and technological prowess. These aspirations were left unrealized due to the true legacy of the Marcoses: driving up international debt for their own gain, looting public coffers, silencing dissent through extrajudicial killings of the administration’s critics. Tabios’ characters embody the near-schizophrenic duality of how Filipinos in exile made sense of the tumultuous Marcos years. We see Marites, a daughter of the country’s elites, nonchalantly brushing off the hardships endured by the common folk, conveniently justifying her family’s focus on continuing to make money, in order to survive. Elmo, on the other hand, risked it all – in his indigenous garb, no less – to take his grievances about the United States’ government complicity in allowing the Marcos dictatorship to flourish despite condemnation from the international community.
Filipinos love a good ghost story, and PAGPAG delivers the frights. Where would we be as a people without messages from beyond the grave, with departed loved ones sending requests on behalf of the living. Yet another distinct characteristic of the Filipino culture is our penchant for humor. There’s plenty of humor and hauntings in PAGPAG's stories; perhaps lightness is necessary to jolt back the reader to a place of hope, family and warmth. Indeed, that’s how many Filipinos survived those ill-fated years of the Marcos regime in the homeland and throughout the diaspora: we relied on family, our love and concern for each other. In PAGPAG, scenes depicting culturally Filipino attitudes toward (sometimes unscrupulous) ways of making a living or helping distant relatives carry the heaviness of guilt, the burden of obligation. Humor and love of each other are what gets us through each moral dilemma.
Originally from Sampaloc and Tondo, Maynila, Maileen Dumelod Hamto works as an equity and inclusion leader in the ancestral lands of the Ute, Arapahoe and Cheyenne. She is pursuing doctoral studies in Leadership for Educational Equity at the University of Colorado Denver, focusing her inquiry on advancing social and organizational change through praxis that centers critical race theory, critical whiteness studies, decoloniality, and liberatory pedagogy.
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2013 is still a long way off yet but there are already a lot of movies that have already set a release date for then. One of those movies is the reboot of the Superman franchise with the new film, Superman: Man of Steel, which has success written all over it.
With fan base surrounding the super hero and with the hugely talented, all star cast signed on, Superman: Man of Steel could well be the must see movie of 2013. The screenplay has written by David S. Goyer, who was involved in the writing process of all three, Christopher Nolan, Batman movies. If that doesn’t scream success then there is definitely something wrong.
Superman: Man of Steel will star Henry Cavill, Amy Adams, Diane Lane and Kevin Costner. It has also been rumoured that Russell Crowe has been offered a role in the movie, while Laurence Fishburne has recently signed on to play Perry White. The Zack Snyder directed movie is set to be released on June 14, 2013.


Sands Regency Casino Owner Announces Developments in $1B Reno Neon Line District
Posted on: October 12, 2021, 02:12h.
Last updated on: October 12, 2021, 02:21h.
Jacobs Entertainment unveiled three components of the company’s $1 billion Reno Neon Line District undertaking in the Nevada city. The company is the owner and operator of the Sands Regency Casino Hotel.
Jacobs Entertainment CEO Jeff Jacobs confirmed over the weekend to the Reno Gazette-Journal that a new condominium complex with 130 units will be developed. The location is just south of its Sands Regency casino, between W. 2nd and 3rd streets. Jacobs says it will develop, own, and lease the condos.
Jacobs additionally announced two apartment projects in the district. One complex will be built just south of W. 5th Street between Washington and Ralston streets. The second apartment building is being targeted further west at the convergence of 4th, Keystone, and 3rd streets.
Major Reno Renovation
Jacobs Entertainment is embarking on one of the largest mixed-use development initiatives in the history of Reno. The casino company unveiled its $1 billion Reno Neon Line District vision in 2019. The company currently operates Sands, as well as Gold Dust West casinos in Reno, Carson City, and Elko, and The Gilpin and Lodge casinos in Black Hawk, Co.
The Neon Line District stretches from downtown Reno’s West Street to Keystone Avenue, and from Interstate 80 south to W. 2nd Street.
Jacobs Entertainment in July entered into an agreement with the city to acquire two parcels in the planned district. The company paid $2.44 million for a parking lot adjacent to Sands Regency, and $631,600 for the vacant 290 Keystone Avenue parcel. Both locations are set to become residential complexes.
Jacobs revealed that the two apartment buildings, once completed, will be offered for sale to interested realty groups. The condo site will remain under the ownership of the casino.
Sands Regency recently underwent a substantial renovation to bring the casino hotel up to date. The property’s Aspen Tower was fully updated in part of a $150 million refurbishing. That budget also included Jacobs purchasing and fully renovating four motels and apartments located in the Reno Neon Line District.
Real Estate Demand
Jacobs Entertainment isn’t fully covering the $1 billion investment number for the Reno Neon Line District.
Jacobs says it will finance a little more than half of the overall budget — or upwards of $500 million. The remaining funding will come by way of other investors, such as real estate developers, plus incentives issued by the city, state, and federal government.
The pedestrian-friendly 20-block city district is primarily designed to accommodate Reno’s growing population. The Nevada City dubbed the “Biggest Little City in the World,” has experienced high housing demand, as corporate giants such as Google, Apple, and Tesla have each opened manufacturing facilities in or near the downtown area.
The Neon Line, once finished, will bring 2,000 new residential units to town. The district is expected to take several years to complete.
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Powerball jackpot reaches $137 million; Mega Millions grows to $22 million; Mississippi Match 5 soars to $384,000
JACKSON, MISS. – Lottery officials are expecting a busy day at their headquarters as 78 Cash 4 players claim their $320,000 in combined winnings from last night’s drawing with the winning combination of 6-6-6-6.
Launched Jan. 10, 2022, Cash 4 is the newest draw-style game from the Mississippi Lottery. The big payout is on the heels of a $1 million payout on Monday from the Jan. 28 Mega Millions® drawing.
Last night’s drawing resulted in 50 top prize-winning $1 tickets, each worth $5,000, and 28 $0.50 tickets, each winning $2,500.
Meanwhile, the jackpots in other draw games continue to gain momentum, led by Saturday’s Powerball® drawing reaching $137 million. Friday’s Mega Millions® drawing is now up to $22 million, while the jackpot for tomorrow night’s Mississippi Match 5 drawing is $384,000.
The Mississippi Lottery also debuted three new scratch-off games Tuesday, including a $5 Wheel of Fortune® ticket, based on the long-running game show. The top prize in the Wheel of Fortune game is $100,000, and the game includes five “Winner’s Choice™” prizes.
The other games released for play Tuesday include the $3 Bingo game and the $2 Lucky Shamrock, with top prizes of $30,000 and $20,000, respectively.
For more information on any of the Mississippi Lottery draw-style or scratch-off games, go to www.mslotteryhome.com.

domain: entertainment


Watching the World Test Championship final with a nervous trepidation, former skipper Brendon McCullum feared that the Black Caps may yet again come close but would not win a world title.
However, McCullum’s joy knew no bounds when Kane Williamson and Ross Taylor took New Zealand past the finish line to be crowned the first ever World Test Champions.
New Zealand handed India an eight-wicket defeat in the rain-affected final to lift the inaugural WTC mace in Southampton on Wednesday.
McCullum was thrilled that the side’s maiden title has come in the traditional format.
“They’ve been on a pretty amazing journey for the last few years and they’ve been so close to tasting the ultimate success,” McCullum told ‘SEN Radio’.
“To do it in the purist form of the game is just something quite…


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Background: Most studies of traumatic intraventricular hemorrhage (tIVH) contain fewer than 25 subjects and are retrospective in design, providing minimal information about the entity and its clinical significance.
Methods: We prospectively enrolled trauma patients from 18 centers in North America in the National Emergency X-Radiography Utilization Study (NEXUS) II if they received an emergent head computed tomography (CT) scan, as determined by the managing physician. Clinical data were collected at the time of enrollment and CT reports were compiled at least 1 month later. We calculated prevalence and demographics of tIVH from the 18 sites, while outcome data were gathered from medical records of patients with tIVH who were seen at any of six sites that participated in the follow-up portion of the study. We considered patients who underwent a neurosurgical intervention or who had a "poor outcome" (Glasgow Outcome Scale score of 1 to 3, death, persistent vegetative state, or severe disability) to have suffered a "combined outcome."
Results: Prevalence of tIVH among all trauma patients who received a head CT was 118 in 8,374, or 1.41%. Among tIVH patients, 70% had a "poor outcome" and 76% had a "combined outcome." A poor outcome appeared to be associated with an abnormal presenting Glasgow Coma Scale score and involvement of the third or fourth ventricle, whereas age appeared to be unrelated. Patients with tIVH and no major associated injury on CT tended to do well; only one patient with isolated tIVH had a poor outcome.
Conclusions: Traumatic IVH is rare and is associated with poor outcomes that seem to be the consequence of associated injuries. Isolated tIVH patients who are clinically well appear to have a functional outcome; we were unable to identify a case of isolated tIVH, combined with a normal neurologic examination, resulting in a poor or combined outcome.


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DoTERRA's research group recently published a new study, adding to its growing list of scientific publications, and this one is a bit unique. First, while most of the previous studies dealt with the biological activity of essential oils, this study examined the quality of sleep and one of doTERRA's newest and most popular dietary supplements. Second, it was a human clinical study conducted here on doTERRA's campus, with our own staff as participants. doTERRA Serenity Restful Complex Softgels were released at the 2016 convention because doTERRA saw the need to address one of the most underappreciated aspects of lifelong health and vitality: sleep.
The need to sleep
Sleep quantity and quality is associated with almost every metric of health and well-being. Recent scientific research has produced an almost endless amount of data on the importance of sleep and health. Meeting recommended sleep guidelines and having good sleep hygiene is associated with increased quality of life and prolonged health.
- It is also directly associated with reduced risk for many health problems.
- Good sleep has been shown to have a positive impact on diet and exercise habits and a direct influence on weight management.
- And for the more than 25% of American adults who do not meet generally recommended guidelines for sleep and more than 9 million who regularly use products to help with sleep, improvement in this area is one thing that could make a big difference in their lives.
Although there are many commercial options and a growing number of herbal and natural alternatives, little research has been done on their safety and effectiveness.
Although there is clinical and experimental research to suggest that consumption of the individual components of doTERRA Serenity Restful Complex Softgels (Lavender essential oil, L-theanine, lemon balm, passion flower, and chamomile) can help in various parameters of sleep quality, what was really needed was human clinical data on the final product.
In the recently published study, doTERRA scientists recruited 62 healthy adults who occasionally had trouble sleeping to put doTERRA Serenity Restful Complex Softgels to the test. Participants were divided into placebo and test groups and subjected to a 6-week randomized, double-blind, placebo-controlled crossover study. The study included a 1-week washout period in which no study products or other sleep aids were used, followed by a 2-week intervention in which participants received either the study product or a placebo, then another 1-week washout, and finally another 2-week intervention that included the opposite product.
During the intervention periods, participants were asked to swallow two softgels every night, 30 minutes before bedtime. Participants and researchers had no knowledge for the product used during the intervention periods. Participants also completed a validated sleep quality assessment questionnaire (Leeds Sleep Evaluation Questionnaire, or LSEQ) prior to the study and at the end of each week during the 6-week study period, as well as a diary containing general information on sleep time, physical activity, caffeine intake and other objective data related to sleep efficiency. A total of 51 participants completed the survey.
The results? If you have already integrated doTERRA Serenity Restful Complex Softgels into your daily supplement regimen, the results of this study will not surprise you. During the intervention periods, including the study product, participants reported (on the LSEQ) statistically significant improvements in falling asleep, balance and coordination upon awakening, ease of awakening and alertness after awakening compared with the placebo and washout periods. Moreover, all parameters evaluated from the sleep diaries, with the exception of duration of awakening, showed better scores when participants took the study product than when they took the placebo, although the differences did not reach statistical significance. No serious side effects were reported either.
Although this study was small-scale and short-term, it provides further clinical evidence in support of previous research suggesting that internal consumption of Lavender essential oil, L-theanine, lemon balm, passion flower, and chamomile can improve the parameters of sleep quality and that doTERRA Serenity Restful Complex Softgels can serve as an effective and more natural alternative to single-component sleep products. To promote the restful sleep you need for optimal health, try incorporating doTERRA Serenity Restful Complex Softgels into your daily bedtime routine.


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DMS Bai Yai Qiu Thai Oolong Tea
€6,50 – €18,70
Bai Yai Qiu Thai Oolong Tea is a large-leaf Oolong tea of medium oxidation from cultivated Assmaica tea plants in north Thailand. The ball-shape rolled Oolong tea pleases with mild aroma and just as smooth taste. At this, the bright yellow cup combines the fresh flavors of green tea with the characteristic mineral notes of large-leaf Oolong teas.
For more informationen please see the product description below.
Our DMS Bai Yai Qiu Thai Oolong Tea is a large-leaf (“Bai Yai”) Oolong tea from cultivated Assamica tea plants in north Thailand. Due to it’s medium degree of oxidation, it pleases with mild aroma and just as smooth taste. At this, the bright yellow cup combines the fresh taste of green teas with the characteristic mineral notes of large-leaf Oolong teas. According to the Taiwanese role model, tea producers in north Thailand also roll their Oolong teas to small balls during processing – one leaf, one ball.
Assamica Tea Trees in North Thailand
In north Thailand, the Camellia Sinensis Assamica has been native for several thousand years already. Before the progressed second half of the 20th century, tea plants grew only as wild tea trees here. At that time, their leaves were picked by some local mountain tribes only. Those had brought the knowledge about tea processing from their original home country of China. Since the 1980’s, the Assamica tea plant is also cultivated in tea gardens. This comes with the common annual cuts for promoting the growth of branches and leaves.
Doi Mae Salong – Center of Tea Cultivation in North Thailand
In Doi Mae Salong, the center of tea cultivation in north Thailand, tea has meanwhile become the major cash crop of the local Chinese migrants and mountain tribes. Here, at altitudes between 1200 and 1600 meters, the tea plant finds optimal conditions. Among these is the climate, consisting of 3 seasons. These are a rainy period, a hot and dry period and a cold period. Notably, Doi Mae Salong is the center of tea cultivation in north Thailand.
For infusing, use water of a temperature around 80-85°C. Just like any Oolong tea, you can principally prepare our DMS Bai Yai Qiu Oolong Tea in two basic ways. Once, this is the 1-infusion method prevailing in the western sphere. To do this, pour 200ml water over 3g of DMS Bai Yai Qiu Oolong Tea and let infuse for 2-3 minutes. Alternatively, you might choose the rather ritual preparation according to the traditional Chinese “Gong Fu Cha”, or tea ceremony. This is about isolating and highlighting individual taste nuances and patterns through a series of infusions. However, compared to western preparation, individual infusions will go with shorter infusion periods at higher dosing.
By the way, you will find Oolong tea from wild growing tea tree in north Thaliand here in Siam Tea Shop:
25g, 50g, 100g