Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

Rating general practitioner consultation performance in cancer care: Does the specialty of assessors matter? A simulated patient study

Background: Patients treated for prostate cancer may present to general practitioners (GPs) for treatment follow up, but may be reticent to have their consultations recorded. Therefore the use of simulated patients allows practitioner consultations to be rated. The aim of this study was to determine whether the speciality of the assessor has an impact on how GP consultation performance is rated. Methods: Six pairs of scenarios were developed for professional actors in two series of consultations by GPs. The scenarios included: chronic radiation proctitis, Prostate Specific Antigen (PSA) ‘bounce’, recurrence of cancer, urethral stricture, erectile dysfunction and depression or anxiety. Participating GPs were furnished with the patient’s past medical history, current medication, prostate cancer details and treatment, details of physical examinations. Consultations were video recorded and assessed for quality by two sets of assessors- a team of two GPs and two Radiation Oncologists deploying the Leicester Assessment Package (LAP). LAP scores by the GPs and Radiation Oncologists were compared. Results: Eight GPs participated. In Series 1 the range of LAP scores by GP assessors was 61%-80%, and 67%-86% for Radiation Oncologist assessors. The range for GP LAP scores in Series 2 was 51%- 82%, and 56%-89% for Radiation Oncologist assessors. Within GP assessor correlations for LAP scores were 0.31 and 0.87 in Series 1 and 2 respectively. Within Radiation Oncologist assessor correlations were 0.50 and 0.72 in Series 1 and 2 respectively. Radiation Oncologist and GP assessor scores were significantly different for 4 doctors and for some scenarios. Anticipatory care was the only domain where GPs scored participants higher than Radiation Oncologist assessors. Conclusion: The assessment of GP consultation performance is not consistent across assessors from different disciplines even when they deploy the same assessment tool

Vortices in polariton OPO superfluids

This chapter reviews the occurrence of quantised vortices in polariton fluids, primarily when polaritons are driven in the optical parametric oscillator (OPO) regime. We first review the OPO physics, together with both its analytical and numerical modelling, the latter being necessary for the description of finite size systems. Pattern formation is typical in systems driven away from equilibrium. Similarly, we find that uniform OPO solutions can be unstable to the spontaneous formation of quantised vortices. However, metastable vortices can only be injected externally into an otherwise stable symmetric state, and their persistence is due to the OPO superfluid properties. We discuss how the currents charactering an OPO play a crucial role in the occurrence and dynamics of both metastable and spontaneous vortices.Comment: 40 pages, 16 figure

The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts

The clinical effects of hypokalemia including action potential prolongation and arrhythmogenicity suppressible by lidocaine were reproduced in hypokalemic (3.0 mM K(+)) Langendorff-perfused murine hearts before and after exposure to lidocaine (10 μM). Novel limiting criteria for local and transmural, epicardial, and endocardial re-excitation involving action potential duration (at 90% repolarization, APD(90)), ventricular effective refractory period (VERP), and transmural conduction time (Δlatency), where appropriate, were applied to normokalemic (5.2 mM K(+)) and hypokalemic hearts. Hypokalemia increased epicardial APD(90) from 46.6 ± 1.2 to 53.1 ± 0.7 ms yet decreased epicardial VERP from 41 ± 4 to 29 ± 1 ms, left endocardial APD(90) unchanged (58.2 ± 3.7 to 56.9 ± 4.0 ms) yet decreased endocardial VERP from 48 ± 4 to 29 ± 2 ms, and left Δlatency unchanged (1.6 ± 1.4 to 1.1 ± 1.1 ms; eight normokalemic and five hypokalemic hearts). These findings precisely matched computational predictions based on previous reports of altered ion channel gating and membrane hyperpolarization. Hypokalemia thus shifted all re-excitation criteria in the positive direction. In contrast, hypokalemia spared epicardial APD(90) (54.8 ± 2.7 to 60.6 ± 2.7 ms), epicardial VERP (84 ± 5 to 81 ± 7 ms), endocardial APD(90) (56.6 ± 4.2 to 63.7 ± 6.4 ms), endocardial VERP (80 ± 2 to 84 ± 4 ms), and Δlatency (12.5 ± 6.2 to 7.6 ± 3.4 ms; five hearts in each case) in lidocaine-treated hearts. Exposure to lidocaine thus consistently shifted all re-excitation criteria in the negative direction, again precisely agreeing with the arrhythmogenic findings. In contrast, established analyses invoking transmural dispersion of repolarization failed to account for any of these findings. We thus establish novel, more general, criteria predictive of arrhythmogenicity that may be particularly useful where APD(90) might diverge sharply from VERP

Evaluation of a joint Bioinformatics and Medical Informatics international course in Peru

Background: New technologies that emerge at the interface of computational and biomedical science could drive new advances in global health, therefore more training in technology is needed among health care workers. To assess the potential for informatics training using an approach designed to foster interaction at this interface, the University of Washington and the Universidad Peruana Cayetano Heredia developed and assessed a one-week course that included a new Bioinformatics (BIO) track along with an established Medical/Public Health Informatics track (MI) for participants in Peru. Methods: We assessed the background of the participants, and measured the knowledge gained by track-specific (MI or BIO) 30-minute pre- and post-tests. Participants' attitudes were evaluated both by daily evaluations and by an end-course evaluation. Results: Forty-three participants enrolled in the course - 20 in the MI track and 23 in the BIO track. Of 20 questions, the mean % score for the MI track increased from 49.7 pre-test (standard deviation or SD = 17.0) to 59.7 (SD = 15.2) for the post-test (P = 0.002, n = 18). The BIO track mean score increased from 33.6 pre-test to 51.2 post-test (P less than 0.001, n = 21). Most comments (76%) about any aspect of the course were positive. The main perceived strength of the course was the quality of the speakers, and the main perceived weakness was the short duration of the course. Overall, the course acceptability was very good to excellent with a rating of 4.1 (scale 1-5), and the usefulness of the course was rated as very good. Most participants (62.9%) expressed a positive opinion about having had the BIO and MI tracks come together for some of the lectures. Conclusion: Pre- and post-test results and the positive evaluations by the participants indicate that this first joint Bioinformatics and Medical/Public Health Informatics (MI and BIO) course was a success.The University of Washington AMAUTA Global Training in Health Informatics, a Fogarty International Center/NIH funded grant (5D43TW007551), and the AMAUTA Research Practica Program, a Puget Sound Partners for Global Health-funded grant

Carotenoid accumulation during tomato fruit ripening is modulated by the auxin-ethylene balance

Background : Tomato fruit ripening is controlled by ethylene and is characterized by a shift in color from green to red, a strong accumulation of lycopene, and a decrease in β-xanthophylls and chlorophylls. The role of other hormones, such as auxin, has been less studied. Auxin is retarding the fruit ripening. In tomato, there is no study of the carotenoid content and related transcript after treatment with auxin. Results : We followed the effects of application of various hormone-like substances to “Mature-Green” fruits. Application of an ethylene precursor (ACC) or of an auxin antagonist (PCIB) to tomato fruits accelerated the color shift, the accumulation of lycopene, α-, β-, and δ-carotenes and the disappearance of β-xanthophylls and chlorophyll b. By contrast, application of auxin (IAA) delayed the color shift, the lycopene accumulation and the decrease of chlorophyll a. Combined application of IAA + ACC led to an intermediate phenotype. The levels of transcripts coding for carotenoid biosynthesis enzymes, for the ripening regulator Rin, for chlorophyllase, and the levels of ethylene and abscisic acid (ABA) were monitored in the treated fruits. Correlation network analyses suggest that ABA, may also be a key regulator of several responses to auxin and ethylene treatments. Conclusions : The results suggest that IAA retards tomato ripening by affecting a set of (i) key regulators, such as Rin, ethylene and ABA, and (ii) key effectors, such as genes for lycopene and β-xanthophyll biosynthesis and for chlorophyll degradation

Association between maternal depression symptoms across the first eleven years of their child’s life and subsequent offspring suicidal ideation

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child’s life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19,4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis

Estimated Comparative Integration Hotspots Identify Different Behaviors of Retroviral Gene Transfer Vectors

Integration of retroviral vectors in the human genome follows non random patterns that favor insertional deregulation of gene expression and may cause risks of insertional mutagenesis when used in clinical gene therapy. Understanding how viral vectors integrate into the human genome is a key issue in predicting these risks. We provide a new statistical method to compare retroviral integration patterns. We identified the positions where vectors derived from the Human Immunodeficiency Virus (HIV) and the Moloney Murine Leukemia Virus (MLV) show different integration behaviors in human hematopoietic progenitor cells. Non-parametric density estimation was used to identify candidate comparative hotspots, which were then tested and ranked. We found 100 significative comparative hotspots, distributed throughout the chromosomes. HIV hotspots were wider and contained more genes than MLV ones. A Gene Ontology analysis of HIV targets showed enrichment of genes involved in antigen processing and presentation, reflecting the high HIV integration frequency observed at the MHC locus on chromosome 6. Four histone modifications/variants had a different mean density in comparative hotspots (H2AZ, H3K4me1, H3K4me3, H3K9me1), while gene expression within the comparative hotspots did not differ from background. These findings suggest the existence of epigenetic or nuclear three-dimensional topology contexts guiding retroviral integration to specific chromosome areas