| 1. |
- Abdallah, Qasem M. A., et al.
(author)
-
Minor structural modifications to alchemix influence mechanism of action and pharmacological activity
- 2012
-
In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 83:11, s. 1514-1522
-
Journal article (peer-reviewed)abstract
- Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumours. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in Cl supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies.
|
|
| 2. |
- Engholm, Gerda, et al.
(author)
-
Colorectal cancer survival in the Nordic countries and the United Kingdom : Excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000
- 2007
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:5, s. 1115-1122
-
Journal article (peer-reviewed)abstract
- A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five-year relative period survival using deaths in 1999-2000 following cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling. Follow-up time since diagnosis with age as an effect-modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow-up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5-5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age-intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies.
|
|
| 3. |
- Farrell, Lisa, et al.
(author)
-
The demand for lotto : the role of conscious selection
- 2000
-
In: Journal of business & economic statistics. - : American Statistical Assoication. - 0735-0015 .- 1537-2707. ; 18:2, s. 228-241
-
Journal article (peer-reviewed)abstract
- This article presents estimates of the elasticity of demand for lottery tickets using time series data in which there is variation in the expected value of a lottery ticket induced by rollovers. An important feature of our data is that there are far more rollovers than expected given the lottery design. We find strong evidence that individuals do not choose their lottery numbers uniformly from a uniform distribution-that is, conscious selection. We use our estimates to derive the inverse supply function for the industry, and this enables us to identify the demand elasticity. We find the price elasticity to be close to unity, which implies that the operator is revenue maximizing-which is the regulator's objective.
|
|
| 4. |
- Hartley, Roger, et al.
(author)
-
Heterogeneous demand responses to discrete price changes : an application to the purchase of lottery tickets
- 2006
-
In: Computational Statistics & Data Analysis. - : Association for Computing Machinery. - 0167-9473 .- 1872-7352. ; 50:3, s. 859-877
-
Journal article (peer-reviewed)abstract
- During the survey period of any household expenditure survey price variations may occur. Such variation can be used to identify heterogeneous demand responses to price changes. This is feasible because expenditure surveys usually contain a large number of observations. The principal difficulty for estimation arises because of the sampling process which generates the data. An estimable model of individual purchase is presented and is estimated in the case of the demand for lottery tickets. This model allows identification of heterogeneous responses to changes in the rollover state (i.e. whether last week's jackpot has been added to the current jackpot). The distribution of heterogeneous responses, in the form of a bivariate mixing distribution, is shown to be identified from the available data. The EM algorithm is used to estimate the parameters of the mixing distribution. The estimates imply that there is substantial heterogeneity in the population both in the normal expenditure levels and in the reaction to a jackpot rolled over.
|
|
| 5. |
- Hartley, Roger, et al.
(author)
-
On the design of lottery games
- 2003
-
In: Journal of the Operational Research Society. - : Palgrave Macmillan. - 0160-5682 .- 1476-9360. ; 54:1, s. 89-100
-
Journal article (peer-reviewed)abstract
- We describe a model of participation in lottery games designed to address the optimisation of tax revenue in state-sponsored lotteries. The model treats participants dynamically and examines a long-run equilibrium. A novel high frequency approximation is used to turn the problem into a static, state-contingent deterministic programming problem. We demonstrate that the solution of this problem has qualitatively plausible properties and then calibrate the model against the United Kingdom National Lottery (UKNL). The results suggest that the current design of the UKNL may not be maximising tax revenue.
|
|
| 6. |
- Lanot, Gauthier, 1965-, et al.
(author)
-
Who really wants to be a millionaire? : estimates of risk aversion from gameshow data
- 2014
-
In: Journal of applied econometrics (Chichester, England). - : John Wiley & Sons. - 0883-7252 .- 1099-1255. ; 29:6, s. 861-879
-
Journal article (peer-reviewed)abstract
- This paper estimates the degree of risk aversion from one of the most popular TV gameshows ever. The format of the show is straightforward; it involves no strategic decision making; we have a large number of observations; and the prizes are cash, which is paid immediately and covers a large range: from 100 pound up to 1 pound million. We provide non-parametric estimates of the utility function and then we test some parametric restrictions. We find that, although the restriction to CRRA utility is statistically rejected, a log function approximates the utility function quite well over a large range of potential winnings.
|
|
