Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Prevalence of Adverse Life Events, Depression and Suicidal Thoughts and Behaviour among a Community Sample of Young People aged 15-24 Years

Objective: To provide prevalence data on several key mental health indicators for young people aged 15 to 24 years. Methods: A cross-sectional household survey, using telephone recruitment followed by a postal pencil-and-paper questionnaire. The overall response rate was 67.3%. Results: Difficulties with interpersonal relationships are common causes of distress for young people, in particular problems with parents, problems with friends and relationship break-ups. Depressive symptomatology is common among young people with approximately one in eight males and one in four females reporting current depressive symptomatology. One in three young people reported that they had had suicidal thoughts at some time in the past, 1.2% of young people reported that they had made a plan on how to kill themselves in the four-week period prior to completing the survey and 6.9% of young people reported that they had tried to kill themselves at some time during their life time (4.2% of males and 9.0% of females). Conclusions and implications: The prevalence figures for the various mental health indicators presented in this paper represent good baseline information upon which to examine the progress over time of interventions designed to improve the mental health of young people.

Patient based method of assessing adverse events in clinical trials in rheumatology: the revised Stanford Toxicity Index

We describe the progress towards developing a patient rated toxicity index that meets all of the patient-important attributes defined by the OMERACT Drug Safety Working Party, These attributes are frequency, severity. importance to patient, importance to the clinician, impact on economics, impact on activities, and integration of adverse effects with benefits. The Stanford Toxicity Index (STI) has been revised to collect all attributes with the exception of impact on activities. However, since the STI is a part of the Health Assessment Questionnaire (HAQ). impact on activities is collected by the HAQ. In particular, a new question asks patients to rate overall satisfaction, taking into consideration both benefits and adverse effects. The nest step in the development of this tool is to ensure that the STI meets the OMERACT filter of truth, discrimination, and feasibility. Although truth and feasibility have been confirmed by comparisons within the ARAMIS database, discrimination needs to be assessed in clinical trials.

Repeated flood events and fossil forests at Curio Bay (Middle Jurassic), New Zealand

During the Middle Jurassic, the regional environment of Curio Bay, southeast South Island, New Zealand, was a fluvial plain marginal to volcanic uplands. Intermittent flashy, poorly-confined flood events buried successive conifer forests. With the termination of each flood, soils developed and vegetation was reestablished. In most cases, this developed into coniferous forest. In approximately 40 m of vertical section, 10 fossil forest horizons can be distinguished, highlighting a type of fluvial architecture which is poorly documented. Flood-basin material is minimal, but a short-Lived floodbasin lake is inferred to have developed within the interval of study. Paleocurrent indicators suggest enclosure of the basin on more than one side. Sedimentation style suggests a relatively dry (less than humid but not arid) climate with seasonal rainfall. (C) 2001 Elsevier Science B.V. All rights reserved.

Characterisation of Leucaena condensed tannins by size and protein precipitation capacity

The ability of differently sized condensed tannins from the genus Leucaena, a fodder tree-legume, to bind protein at different pH values was evaluated to characterise their potential biological effects. Two factors affecting the ability of condensed tannin to bind protein, its major biological activity, have been purported to be the condensed tannin size and the pH of the reaction environment. To test these hypotheses, the protein-precipitating capacities of condensed tannin extracted from four Leucaena genotypes, L leucocephala (UHK636), L pallida (CQ3439), L trichandra (CP146568) and L collinsii (OFI52/88), were assessed. Condensed tannin from L leucocephala had approximately 50% of the ability to precipitate protein on a gg(-1) basis than L pallida or L trichandra, while L collinsii gave no measurable ability to precipitate protein (reaction environment pH 5.0). Increasing or decreasing the pH of the reaction solution away from pH 5.0 (approximately the isoelectric point of the protein) reduced the ability of condensed tannin from all the species to precipitate protein, the decrease being higher at pH 2.5 than at pH 7.5. Condensed tannins from each Leucaena species were also separated by size exclusion chromatography, and the fractions examined for protein-precipitating capacity. In general, it was found that the larger-sized condensed tannin of the accessions L pallida and L trichandra could precipitate more protein than the smaller-sized condensed tannin. This pattern was not found for L leucocephala. (C) 2001 Society of Chemical Industry.

Precipitation hardening of Cu-Fe-Cr alloys - Part I - Mechanical and electrical properties

This research is part of a project whose scope was to investigate the engineering properties of new non-commercial alloy formulations based on the Cu rich corner of the Cu-Fe-Cr ternary system with the primary aim of exploring the development of a new cost-effective high-strength, high-conductivity copper alloy. The literature indicated that Cu rich Cu-Cr and Cu-Fe alloys have been thoroughly investigated. A number of commercial alloys have been developed and these are used for a variety of applications requiring combinations of high-strength, high-conductivity and resistance to softening. Little evidence was found in the literature that the Cu rich corner of the Cu-Fe-Cr system had previously been investigated for the purpose of developing high-strength, high-conductivity copper alloys resistant to softening. The aim of these present investigations was to explore the possibility that new alloys could be developed that combined the properties of both sets of alloys, ie large precipitation hardening response combined with the ability to stabilise cold worked microstructures to high temperatures while at the same maintain high electrical conductivity. To assess the feasibility of this goal the following alloys were chosen for investigation: Cu-0.7wt%Cr-0.3wt%Fe, Cu-0.7wt%Cr-0.8wt%Fe, Cu-0.7wt%Cr-2.0wt%Fe. This paper reports on the mechanical property investigation which indicated that the Cu-0.7wt%Cr-0.3wt%Fe, and Cu-0.7wt%Cr-2.0wt%Fe alloys were worthy of further investigation. (C) 2001 Kluwer Academic Publishers.

Precipitation hardening of Cu-Fe-Cr alloys - Part II - Microstructural characterisation

This research is part of a project whose scope was to investigate the engineering properties of new non-commercial alloy formulations based on the Cu rich corner of the Cu-Fe-Cr ternary system with the primary aim of exploring the development of a new cost-effective high-strength, high-conductivity copper alloy. Promising properties have been measured for the following alloys: Cu-0.7wt%Cr-0.3wt%Fe and Cu-0.7wt%Cr-2.0wt%Fe. This paper reports on the microstructural characterisation of these alloys and discusses the mechanical and electrical properties of these alloys in terms of their microstructure, particularly the formation of precipitates. These alloys have evinced properties that warrant further investigation. Cost modelling has shown that Cu-0.7wt%Cr-0.3wt%Fe is approximately 25% cheaper to produce than commercial Cu-1%Cr. It has also been shown to be more cost efficient on a yield stress and % IACS per dollar basis. The reason for the cost saving is that the Cu-0.7%Cr-0.3%Fe alloy can be made with low carbon ferro-chrome additions as the source of chromium rather than the more expensive Cu-Cr master-alloy. For applications in which cost is one of the primary materials selection criteria, it is envisaged that there would be numerous applications in both cast and wrought form, where the Cu-0.7%Cr-0.3%Fe alloy would be more suitable than Cu-1%Cr. (C) 2001 Kluwer Academic Publishers.

Lipid-lowering therapy following major cardiac events: progress and deficits

Objective: To assess hospital prescribing of lipid-lowering agents in a tertiary hospital, and examine continuation of, or changes to, such therapy in the 6-18 months following discharge. Design: Retrospective data extraction from the hospital records of patients admitted from October 1998 to April 1999. These patients and their general practitioners were then contacted to obtain information about ongoing management after discharge. Setting: Tertiary public hospital and community. Participants: 352 patients admitted to hospital with acute myocardial infarction or unstable angina, and their GPs. Main outcome measures: Percentage of eligible patients discharged on lipid-lowering therapy and percentage of patients continuing or starting such therapy 6-18 months after discharge. Results: 10% of inpatients with acute coronary syndromes did not have lipid-level estimations performed or arranged during admission. Documentation of lipid levels in discharge summaries was poor. Eighteen per cent of patients with a total serum cholesterol level greater than 5.5 mmol/L did not receive a discharge prescription for a cholesterol-lowering agent. Compliance with treatment on follow-up was 88% in the group discharged on treatment. However, at follow-up, 70% of patients discharged without therapy had not been commenced on lipid-lowering treatment by their GPs. Conclusions: Prescribing of lipid-lowering therapy for secondary prevention following acute coronary syndromes remains suboptimal. Commencing treatment in hospital is likely to result in continuing therapy in the community. Better communication of lipid-level results, treatment and treatment aims between hospitals and GPs might encourage optimal treatment practices.

Genetic consequences of sequential founder events by an island-colonizing bird

The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documented, natural colonization events by the silvereye species-complex (Zosterops lateralis), a group used to illustrate the process of island colonization in the original founder effect model. Our results indicate that single founder events do not affect levels of heterozygosity or allelic diversity, nor do they result in immediate genetic differentiation between populations. Instead, four to five successive founder events are required before indices of diversity and divergence approach that seen in evolutionarily old forms. A Bayesian analysis based on computer simulation allows inferences to be made on the number of effective founders and indicates that founder effects are weak because island populations are established from relatively large flocks. Indeed, statistical support for a founder event model was not significantly higher than for a gradual-drift model for all recently colonized islands. Taken together, these results suggest that single colonization events in this species complex are rarely accompanied by severe founder effects, and multiple founder events and/or long-term genetic drift have been of greater consequence for neutral genetic diversity.