Review of pyronaridine anti-malarial properties and product characteristics.

Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure

Incidence and survival for cancer in children and young adults in the North of England, 1968–1995: a report from the Northern Region Young Persons’ Malignant Disease Registry

The Northern Region Young Persons’ Malignant Disease Registry records information on young people under 25 years old diagnosed with cancer in the Northern Region of England. Incidence and survival rates were calculated for children and young adults diagnosed with cancer between 1968 and 1995. There were 2099 (M:F 1.28:1) children (age 0–14 years) and 2217 (M:F 1.23:1) young adults (15–24 years) diagnosed with a first cancer between 1968 and 1995. The age-standardized rate (ASR) for childhood cancer was 121 per million 0 to 14 year-olds per year. For young adults the ASR was 175 per million 15 to 24 year-olds, per year. Incidence of childhood cancer increased over time at a rate of 12 extra cases per million children, per decade (P< 0.001). In young adults incidence rates increased by 16 extra cases per million 15 to 24 year-olds, per decade (P< 0.001). For childhood cancer 5-year survival was 42% for those diagnosed 1968–1977, 57% for 1978–1987 and 71% (95% CI 67–75) for 1988–1995. Survival for young adults over the three periods was 45%, 62% and 73% (95% CI 70–78) respectively. The cumulative risk of developing cancer before the age of 25 is 1 in 285. Over the 28-year period there were significant improvements in survival and modest increases in incidence in both children and young adults. © 2000 Cancer Research Campaig

Comprehensive test ban treaty international monitoring system security threats and proposed security attributes

To monitor compliance with a Comprehensive Test Ban Treaty (CTBT), a sensing network, referred to as the International Monitoring System (IMS), is being deployed. Success of the IMS depends on both its ability to preform its function and the international community`s confidence in the system. To ensure these goals, steps must be taken to secure the system against attacks that would undermine it; however, it is not clear that consensus exists with respect to the security requirements that should be levied on the IMS design. In addition, CTBT has not clearly articulated what threats it wishes to address. This paper proposes four system-level threats that should drive IMS design considerations, identifies potential threat agents, and collects into one place the security requirements that have been suggested by various elements of the IMS community. For each such requirement, issues associated with the requirement are identified and rationale for the requirement is discussed

Statistical Confirmation of Empirical Observations Concerning Tool Mark Striae

Toolmarks produced by 44 sequentially manufactured screwdriver tips have been characterized for surface roughness using a profilometer. Toolmarks were produced in lead at angles of 30°, 60°, and 85°. A computer program developed to compare and match the profilometer data has been used to show that marks from a single tip produced at similar angles yield much higher correlation values than marks produced from the same tip but at different angles. This analysis provides statistical support for the widely-accepted empirical observation that toolmark striae must be reproduced at similar angles in order to be unambiguously identified as being made by a particular tool

Use of a scanning optical profilometer for toolmark characterization

An optical profilometer has been used to obtain 3-dimensional data for use in two research projects concerning toolmark quantification and identification. In the first study quantitative comparisons between toolmarks made using data from the optical system proved superior to similar data obtained using a stylus profilometer. In the second study the ability of the instrument to obtain accurate data from two surfaces intersecting at a high angle (approximately 90 degrees) is demonstrated by obtaining measurements from the tip of a flat screwdriver. The data obtained was used to produce a computer generated virtual tool, which was then employed to create virtual tool marks. How these experiments were conducted and the results obtained will be presented and discussed

Asset liability modelling and pension schemes: the application of robust optimization to USS

This paper uses a novel numerical optimization technique - robust optimization - that is well suited to solving the asset-liability management (ALM) problem for pension schemes. It requires the estimation of fewer stochastic parameters, reduces estimation risk and adopts a prudent approach to asset allocation. This study is the first to apply it to a real-world pension scheme, and the first ALM model of a pension scheme to maximise the Sharpe ratio. We disaggregate pension liabilities into three components - active members, deferred members and pensioners, and transform the optimal asset allocation into the scheme’s projected contribution rate. The robust optimization model is extended to include liabilities and used to derive optimal investment policies for the Universities Superannuation Scheme (USS), benchmarked against the Sharpe and Tint, Bayes-Stein, and Black-Litterman models as well as the actual USS investment decisions. Over a 144 month out-of-sample period robust optimization is superior to the four benchmarks across 20 performance criteria, and has a remarkably stable asset allocation – essentially fix-mix. These conclusions are supported by six robustness checks