Trends in the lifetime risk of developing cancer in Great Britain: comparison of risk for those born from 1930 to 1960

BACKGROUND: Typically, lifetime risk is calculated by the period method using current risks at different ages. Here, we estimate the probability of being diagnosed with cancer for individuals born in a given year, by estimating future risks as the cohort ages. METHODS: We estimated the lifetime risk of cancer in Britain separately for men and women born in each year from 1930 to 1960. We projected rates of all cancers (excluding non-melanoma skin cancer) and of all cancer deaths forwards using a flexible age-period-cohort model and backwards using age-specific extrapolation. The sensitivity of the estimated lifetime risk to the method of projection was explored. RESULTS: The lifetime risk of cancer increased from 38.5% for men born in 1930 to 53.5% for men born in 1960. For women it increased from 36.7 to 47.5%. Results are robust to different models for projections of cancer rates. CONCLUSIONS: The lifetime risk of cancer for people born since 1960 is >50%. Over half of people who are currently adults under the age of 65 years will be diagnosed with cancer at some point in their lifetime

Building development and roads: implications for the distribution of stone curlews across the Brecks

Background: Substantial new housing and infrastructure development planned within England has the potential to conflict with the nature conservation interests of protected sites. The Breckland area of eastern England (the Brecks) is designated as a Special Protection Area for a number of bird species, including the stone curlew (for which it holds more than 60% of the UK total population). We explore the effect of buildings and roads on the spatial distribution of stone curlew nests across the Brecks in order to inform strategic development plans to avoid adverse effects on such European protected sites. Methodology: Using data across all years (and subsets of years) over the period 1988 – 2006 but restricted to habitat areas of arable land with suitable soils, we assessed nest density in relation to the distances to nearest settlements and to major roads. Measures of the local density of nearby buildings, roads and traffic levels were assessed using normal kernel distance-weighting functions. Quasi-Poisson generalised linear mixed models allowing for spatial auto-correlation were fitted. Results: Significantly lower densities of stone curlew nests were found at distances up to 1500m from settlements, and distances up to 1000m or more from major (trunk) roads. The best fitting models involved optimally distance-weighted variables for the extent of nearby buildings and the trunk road traffic levels. Significance : The results and predictions from this study of past data suggests there is cause for concern that future housing development and associated road infrastructure within the Breckland area could have negative impacts on the nesting stone curlew population. Given the strict legal protection afforded to the SPA the planning and conservation bodies have subsequently agreed precautionary restrictions on building development within the distances identified and used the modelling predictions to agree mitigation measures for proposed trunk road developments

A bidentate Polycomb Repressive-Deubiquitinase complex is required for efficient activity on nucleosomes

Attachment of ubiquitin to lysine 119 of Histone 2A (H2AK119Ub) is an epigenetic mark characteristic of repressed developmental genes, which is removed by the Polycomb Repressive-Deubiquitinase (PR-DUB) complex. Here we report the crystal structure of the Drosophila PR-DUB, revealing that the deubiquitinase Calypso and its activating partner ASX form a 2:2 complex. The bidentate Calypso–ASX complex is generated by dimerisation of two activated Calypso proteins through their coiled-coil regions. Disrupting the Calypso dimer interface does not affect inherent catalytic activity, but inhibits removal of H2AK119Ub as a consequence of impaired recruitment to nucleosomes. Mutating the equivalent surface on the human counterpart, BAP1, also compromises activity on nucleosomes. Together, this suggests that high local concentrations drive assembly of bidentate PR-DUB complexes on chromatin—providing a mechanistic basis for enhanced PR-DUB activity at specific genomic foci, and the impact of distinct classes of PR-DUB mutations in tumorigenesis

A Mitochondrial DNA Phylogeny Indicates Close Relationships between Populations of Lutzomyia whitmani (Diptera: Psychodidae, Phlebotominae) from the Rain-forest Regions of Amazônia and Northeast Brazil

Phylogenetic analysis of all 31 described mitochondrial (cytochrome b) haplotypes of Lutzomyia whitmani demonstrated that new material from the State of Rondônia, in southwest Amazônia, forms a clade within a lineage found only in the rain-forest regions of Brazil. This rain-forest lineage also contains two other clades of haplotypes, one from eastern Amazônia and one from the Atlantic forest zone of northeast Brazil (including the type locality of the species in Ilhéus, State of Bahia). These findings do not favour recognizing two allopatric cryptic species of L. whitmani, one associated with the silvatic transmission of Leishmania shawi in southeast Amazônia and the other with the peridomestic transmission of Le. braziliensis in northeast Brazil. Instead, they suggest that there is (or has been in the recent past) a continuum of inter-breeding populations of L. whitmani in the rain-forest regions of Brazil

Feeding Preferences and the Nutritional Value of Tropical Algae for the Abalone Haliotis asinina

Understanding the feeding preferences of abalone (high-value marine herbivores) is integral to new species development in aquaculture because of the expected link between preference and performance. Performance relates directly to the nutritional value of algae – or any feedstock – which in turn is driven by the amino acid content and profile, and specifically the content of the limiting essential amino acids. However, the relationship between feeding preferences, consumption and amino acid content of algae have rarely been simultaneously investigated for abalone, and never for the emerging target species Haliotis asinina. Here we found that the tropical H. asinina had strong and consistent preferences for the red alga Hypnea pannosa and the green alga Ulva flexuosa, but no overarching relationship between protein content (sum of amino acids) and preference existed. For example, preferred Hypnea and Ulva had distinctly different protein contents (12.64 vs. 2.99 g 100 g−1) and the protein-rich Asparagopsis taxiformis (>15 g 100 g−1 of dry weight) was one of the least preferred algae. The limiting amino acid in all algae was methionine, followed by histidine or lysine. Furthermore we demonstrated that preferences can largely be removed using carrageenan as a binder for dried alga, most likely acting as a feeding attractant or stimulant. The apparent decoupling between feeding preference and algal nutritive values may be due to a trade off between nutritive values and grazing deterrence associated with physical and chemical properties

Future possibilities in the prevention of breast cancer: Breast cancer prevention trials

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed, of which three have reported efficacy results. A fifth trial using raloxifene has also been reported. The largest tamoxifen trial showed approximately 50% reduction in breast cancer incidence in the short term, but the two smaller trials did not find any reduction. Greater agreement exists for side effects; incidences of thromboembolic disease and endometrial cancers are raised approximately threefold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a meta-analysis indicates that all results are compatible with a 40% reduction in short-term incidence. Several important questions remain regarding the clinical implications of this result, including the effect on mortality, the appropriate risk groups for chemoprevention and the long-term effects on incidence. Continued follow up of these trials is crucial for resolving these issues

Cytomegalovirus Viremia as a Risk Factor for Mortality Prior to Antiretroviral Therapy among HIV-Infected Gold Miners in South Africa

BACKGROUND: Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV. METHODS: Using a cohort of mineworkers with stored plasma samples, we investigated the association between CMV DNA concentration and mortality prior to antiretroviral therapy availability. RESULTS: Among 1341 individuals (median CD4 count 345 cells/µl, 70% WHO stage 1 or 2, median follow-up 0.9 years), 70 (5.2%) had CMV viremia at baseline; 71 deaths occurred. In univariable analysis CMV viremia at baseline was associated with a three-fold increase in mortality (hazard ratio [HR] 3.37; 95% confidence intervals [CI] 1.60, 7.10). After adjustment for CD4 count, WHO stage and HIV viral load (N = 429 with complete data), the association was attenuated (HR 2.27; 95%CI 0.88, 5.83). Mortality increased with higher CMV viremia (≥1,000 copies/ml vs. no viremia, adjusted HR 3.65, 95%CI: 1.29, 10.41). Results were similar using time-updated CMV viremia. CONCLUSIONS: High copy number, subclinical CMV viremia was an independent risk factor for mortality among male HIV-infected adults in South Africa with relatively early HIV disease. Studies to determine whether anti-CMV therapy to mitigate high copy number viremia would increase lifespan are warranted

Interrater reliability of the mind map assessment rubric in a cohort of medical students

<p>Abstract</p> <p>Background</p> <p>Learning strategies are thinking tools that students can use to actively acquire information. Examples of learning strategies include mnemonics, charts, and maps. One strategy that may help students master the tsunami of information presented in medical school is the mind map learning strategy. Currently, there is no valid and reliable rubric to grade mind maps and this may contribute to their underutilization in medicine. Because concept maps and mind maps engage learners similarly at a metacognitive level, a valid and reliable concept map assessment scoring system was adapted to form the mind map assessment rubric (MMAR). The MMAR can assess mind map depth based upon concept-links, cross-links, hierarchies, examples, pictures, and colors. The purpose of this study was to examine interrater reliability of the MMAR.</p> <p>Methods</p> <p>This exploratory study was conducted at a US medical school as part of a larger investigation on learning strategies. Sixty-six (<it>N </it>= 66) first-year medical students were given a 394-word text passage followed by a 30-minute presentation on mind mapping. After the presentation, subjects were again given the text passage and instructed to create mind maps based upon the passage. The mind maps were collected and independently scored using the MMAR by 3 examiners. Interrater reliability was measured using the intraclass correlation coefficient (<it>ICC</it>) statistic. Statistics were calculated using SPSS version 12.0 (Chicago, IL).</p> <p>Results</p> <p>Analysis of the mind maps revealed the following: concept-links <it>ICC </it>= .05 (95% CI, -.42 to .38), cross-links <it>ICC </it>= .58 (95% CI, .37 to .73), hierarchies <it>ICC </it>= .23 (95% CI, -.15 to .50), examples <it>ICC </it>= .53 (95% CI, .29 to .69), pictures <it>ICC </it>= .86 (95% CI, .79 to .91), colors <it>ICC </it>= .73 (95% CI, .59 to .82), and total score <it>ICC </it>= .86 (95% CI, .79 to .91).</p> <p>Conclusion</p> <p>The high <it>ICC </it>value for total mind map score indicates strong MMAR interrater reliability. Pictures and colors demonstrated moderate to strong interrater reliability. We conclude that the MMAR may be a valid and reliable tool to assess mind maps in medicine. However, further research on the validity and reliability of the MMAR is necessary.</p