Ethics in neuroscience graduate training programs:Views and models from Canada

Consideration of the ethical, social, and policy implications of research has become increasingly important to scientists and scholars whose work focuses on brain and mind, but limited empirical data exist on the education in ethics available to them. We examined the current landscape of ethics training in neuroscience programs, beginning with the Canadian context specifically, to elucidate the perceived needs of mentors and trainees and offer recommendations for resource development to meet those needs. We surveyed neuroscientists at all training levels and interviewed directors of neuroscience programs and training grants. A total of 88% of survey respondents reported general interest in ethics, and 96% indicated a desire for more ethics content as it applies to brain research and clinical translation. Expert interviews revealed formal ethics education in over half of programs and in 90% of grants-based programs. Lack of time, resources, and expertise, however, are major barriers to expanding ethics content in neuroscience education. We conclude with an initial set of recommendations to address these barriers which includes the development of flexible, tailored ethics education tools, increased financial support for ethics training, and strategies for fostering collaboration between ethics experts, neuroscience program directors, and funding agencies. © 2010 the Authors. Journal Compilation © 2010 International Mind, Brain, and Education Society and Blackwell Publishing, Inc.

Shared common variants in prostate cancer and blood lipids

BACKGROUND: Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors.

METHODS: We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n=50 000) and CVD risk factors (n=200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR.

RESULTS: We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR <0.01). For T2D, we detected one locus adjacent to HNF1B.

CONCLUSIONS: We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership: a primary care vignette survey

OBJECTIVES: The International Cancer Benchmarking Partnership (ICBP) is a collaboration between 6 countries and 12 jurisdictions with similar primary care-led health services. This study investigates primary care physician (PCP) behaviour and systems that may contribute to the timeliness of investigating for cancer and subsequently, international survival differences.

DESIGN: A validated survey administered to PCPs via the internet set out in two parts: direct questions on primary care structure and practice relating to cancer diagnosis, and clinical vignettes, assessing management of scenarios relating to the diagnosis of lung, colorectal or ovarian cancer.

PARTICIPANTS: 2795 PCPs in 11 jurisdictions: New South Wales and Victoria (Australia), British Columbia, Manitoba, Ontario (Canada), England, Northern Ireland, Wales (UK), Denmark, Norway and Sweden.

PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis compared the cumulative proportion of PCPs in each jurisdiction opting to investigate or refer at each phase for each vignette with 1-year survival, and conditional 5-year survival rates for the relevant cancer and jurisdiction. Logistic regression was used to explore whether PCP characteristics or system differences in each jurisdiction affected the readiness to investigate.

RESULTS: 4 of 5 vignettes showed a statistically significant correlation (p<0.05 or better) between readiness to investigate or refer to secondary care at the first phase of each vignette and cancer survival rates for that jurisdiction. No consistent associations were found between readiness to investigate and selected PCP demographics, practice or health system variables.

CONCLUSIONS: We demonstrate a correlation between the readiness of PCPs to investigate symptoms indicative of cancer and cancer survival rates, one of the first possible explanations for the variation in cancer survival between ICBP countries. No specific health system features consistently explained these findings. Some jurisdictions may consider lowering thresholds for PCPs to investigate for cancer-either directly, or by specialist referral, to improve outcomes.

Unconditional constants and polynomial inequalities

If P is a polynomial on Rm of degree at most n then we define the polynomial |P|. Now if B is a convex compact set in Rm, we define the norm ||P||B of P as the maximum of P on B, and then we investigate the inequality || |P| ||B

Modeling Multivariate Interest Rates Using Time-Varying Copulas and Reducible Nonlinear Stochastic Differential Equations

We propose a new approach for modeling nonlinear multivariate interest rate processes based on time-varying copulas and reducible stochastic differential equations (SDEs). In the modeling of the marginal processes, we consider a class of nonlinear SDEs that are reducible to Ornstein--Uhlenbeck (OU) process or Cox, Ingersoll, and Ross (1985) (CIR) process. The reducibility is achieved via a nonlinear transformation function. The main advantage of this approach is that these SDEs can account for nonlinear features, observed in short-term interest rate series, while at the same time leading to exact discretization and closed-form likelihood functions. Although a rich set of specifications may be entertained, our exposition focuses on a couple of nonlinear constant elasticity volatility (CEV) processes, denoted as OU-CEV and CIR-CEV, respectively. These two processes encompass a number of existing models that have closed-form likelihood functions. The transition density, the conditional distribution function, and the steady-state density function are derived in closed form as well as the conditional and unconditional moments for both processes. In order to obtain a more flexible functional form over time, we allow the transformation function to be time varying. Results from our study of U.S. and UK short-term interest rates suggest that the new models outperform existing parametric models with closed-form likelihood functions. We also find the time-varying effects in the transformation functions statistically significant. To examine the joint behavior of interest rate series, we propose flexible nonlinear multivariate models by joining univariate nonlinear processes via appropriate copulas. We study the conditional dependence structure of the two rates using Patton (2006a) time-varying symmetrized Joe--Clayton copula. We find evidence of asymmetric dependence between the two rates, and that the level of dependence is positively related to the level of the two rates. (JEL: C13, C32, G12) Copyright The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org, Oxford University Press.

'Conditional candour' and 'knowing me': an interpretive description study on patient preferences for physician behaviours during end-of-life communication

OBJECTIVE: To understand patients' preferences for physician behaviours during end-of-life communication.

METHODS: We used interpretive description methods to analyse data from semistructured, one-on-one interviews with patients admitted to general medical wards at three Canadian tertiary care hospitals. Study recruitment took place from October 2012 to August 2013. We used a purposive, maximum variation sampling approach to recruit hospitalised patients aged ≥55 years with a high risk of mortality within 6-12 months, and with different combinations of the following demographic variables: race (Caucasian vs non-Caucasian), gender and diagnosis (cancer vs non-cancer).

RESULTS: A total of 16 participants were recruited, most of whom (69%) were women and 70% had a non-cancer diagnosis. Two major concepts regarding helpful physician behaviour during end-of-life conversations emerged: (1) 'knowing me', which reflects the importance of acknowledging the influence of family roles and life history on values and priorities expressed during end-of-life communication, and (2) 'conditional candour', which describes a process of information exchange that includes an assessment of patients' readiness, being invited to the conversation, and sensitive delivery of information.

CONCLUSIONS: Our findings suggest that patients prefer a nuanced approach to truth telling when having end-of-life discussions with their physician. This may have important implications for clinical practice and end-of-life communication training initiatives.