Synthesis, physicochemical and pharmacokinetic studies of potential prodrugs of β-L-2'-deoxycytidine, a selective and specific anti-HBV agent

β-L-2′-Deoxycytidine (β-L-dC) is a potent, selective and specific anti-hepatitis B virus (HBV) agent. To improve its oral bioavailability, several derivatives involving sugar or base acylation, as well as N4-derivatization with an N,N-(dimethyl-amino)methylene function, were synthesized. The physicochemical characteristics (including chemical stabilities, solubilities and distribution coefficient values) and pharmacokinetics of these compounds were determined and compared with those of the parent drug, β-L-dC. Presented in part at the 14th International Conference on Antiviral Research, Seattle, Washington, USA, 8–13 April 2001. Antiviral Reseach 2001; 50:A79

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A Fieldwalking Survey of the Proposed A14 route between Ellington and Girton

Fieldwalking was undertaken along the route of proposed improvements to the A14 road on behalf of Costain Skanska Joint Venture for the Highways Agency. The fieldwalking was divided into two phases, which aimed to first identify and then investigate potential archaeological sites along the planned route. The first phase of fieldwalking comprised a double line transect which was walked along the part of the proposed route between Ellington and Girton This work was undertaken in order to identify artefact scatters indicative of potential archaeological sites that would be examined by the second phase, a more detailed grid walking for total area collection. During the transect phase, three main areas were identified as having a higher than average number of finds that warranted further investigation as potential archaeological sites. Evidence for Mesolithic/Neolithic, Bronze Age, Roman, Saxon, and Medieval activity was recorded within three site

Children’s understanding of natural hazards in Christchurch reflecting on a 2003 study /

In 2003 Cobham Intermediate School student, Sarah Standring, teamed up with our research team as part of her school science project, to collect data on her fellow students understanding of natural hazards in Christchurch (Finnis et al. 2004). Using a questionnaire that had recently been used in an Auckland study, she surveyed over 100 of her classmates to investigate natural hazards risk perceptions, levels of preparedness and participation in hazards education programs. The results of the Cobham survey showed students had high awareness of many hazards, with over half ranking earthquakes as one of the two most likely. Over three quarters reported having felt an earthquake in the past

Children's understanding of natural hazards in Christchurch, New Zealand

Children need to understand and be prepared for natural hazard events as much as adults. Children are vectors of hazard education, having the ability to educate those around them. This study investigated natural hazard risk perceptions, levels of preparedness and participation in education programmes of children from a school in Christchurch, New Zealand. Although hazard education programmes had been attended by a majority of the children hazard awareness was only fair and reported levels of household preparedness were low. Continuing hazards education is needed to increase understanding of hazards and to improve household preparation in the Christchurch community

Trends in prevalence of symptoms of asthma, hay fever, and eczema in 12-14 year olds in the British Isles, 1995-2002: questionnaire survey

The prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children in the United Kingdom ranks among the highest in the world.The evidence from most repeat surveys is that prevalence has increased over the past three decades,2 but the most recent of these studies observed that from 1991 to 1998 the increase was confined to milder symptoms of asthma.3 Since the early 1990s the incidence of asthma episodes presenting to general practitioners, and of hospital admissions, has fallen substantiall