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.

Debating Darwin at the Cape

This paper focuses attention on the fortunes of Darwin's theory among the English-speaking community in Cape Colony during the latter part of the nineteenth century. The paper begins with a review of early encounters with Darwin dwelling particularly on the response of figures like Roderick Noble - professor and editor of the Cape Monthly Magazine, the geologist John Shaw, and Sir Henry Barkly, governor of the colony. Besides these more theoretical responses, Darwin's ideas were also mobilised in a range of scientific inquiries on such subjects as birds and butterflies. But most conspicuous was the use of evolutionary thought-forms in the work of the eminent philologist Wilhelm Bleek, cousin of Darwin's leading German apologist, Ernst Haeckel. The prevailing sense is of a liberal intelligentsia calmly interacting with a novel theory with all due deference. During the 1870s, an address by Langham Dale at the South African Public Library injected new energy into the Darwin discussion. Dale expressed disquiet over some of the anthropological implications of evolution as well as its apparent reductionism, and this stimulated a range of reactions. Several anonymous commentators responded but the most sustained evaluation of Dale's position emanated from the Queenstown physician and later politician, Sir William Bisset Berry. Then, in 1874, copious extracts from John Tyndall's infamous 'Belfast Address' were printed in the Cape Monthly and this added yet further impetus to the debate. Tyndall's seeming materialism bothered a number of readers, not least Hon William Porter, former attorney-general of Cape Colony. To figures like these the materialist extrapolations of radical Darwinians such as Haeckel were deeply disturbing, not just for religious reasons, but because they seemed to destabilise the moral and pedagogic progressivism that lay at the heart of their civilising credo. While reservations about Darwin's proposals were certainly audible, taken in the round Darwinian conversations among the English-speaking literati at the Cape were conducted with liberal sentiments, not least when evolutionary science approached questions of race. For Darwin's writings were seen to confirm a monogenetic account of the origin and unity of the human race, and could readily be called upon to justify the paternalistic ideology that governed colonial affairs.

Does mothers' postnatal depression influence the development of imitation?

Background: Links between mothers' postnatal depression (PND) and children's cognition have been identified in several samples, but the evidence is inconsistent. We hypothesized that PND may specifically interfere with infants' imitation, an early learning ability that features in early mother-infant interaction and is linked to memory, causal understanding and joint attention. 

Methods: A randomly controlled experiment on imitation was embedded into a longitudinal study of a representative sample of firstborn British infants, whose mothers were assessed for depression using the SCAN interview during pregnancy and at 6 months postpartum. At a mean of 12.8 months, 253 infants were presented with two imitation tasks that varied in difficulty, in counterbalanced order. 

Results: The infants of mothers who experienced PND were significantly less likely than other infants in the sample to imitate the modelled actions, showing a 72% reduction in the likelihood of imitation. The association with PND was not explained by sociodemographic adversity, or a history of depression during pregnancy or prior to conception. Mothers' references to infants' internal states during mother-infant interaction at 6 months facilitated imitation at 12 months, but did not explain the link with PND. 

Conclusions: The findings support the hypothesis that associations between PND and later cognitive outcomes may partly derive from effects of the mother's illness on infants' early learning abilities. Support for infants' learning should be considered as an age-appropriate, child-focused component of interventions designed to ameliorate the effects of PND.

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.

Introducing the CTA concept

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. © 2013 Elsevier B.V. All rights reserved.

Predicting intention to work with social robots

The growing number of robotic solutions geared to interact socially with humans, social robots, urge the study of the factors that will facilitate or hinder future human robot collaboration. Hence the research question: what are the factors that predict intention to work with a social robot in the near future. To answer this question the following socio-cognitive models were studied, the theory of reasoned action, the theory of planned behavior and the model of goal directed behavior. These models purport that all the other variables will only have an indirect effect on behavior. That is, through the variables of the model. Based on the research on robotics and social perception/ cognition, social robot appearance, belief in human nature uniqueness, perceived warmth, perceived competence, anthropomorphism, negative attitude towards robots with human traits and negative attitudes towards interactions with robots were studied for their effects on attitude towards working with a social robot, perceived behavioral control, positive anticipated emotions and negative anticipated emotions. Study 1 identified the social representation of robot. Studies 2 to 5 investigated the psychometric properties of the Portuguese version of the negative attitude towards robots scale. Study 6 investigated the psychometric properties of the belief in human nature uniqueness scale. Study 7 tested the theory of reasoned action and the theory of planned behavior. Study 8 tested the model of goal directed behavior. Studies 7 and 8 also tested the role of the external variables. Study 9 tested and compared the predictive power of the three socio-cognitive models. Finally conclusion are drawn from the research results, and future research suggestions are offered.

A Concert of American Music, February 9, 1964

Concert Program for A Concert of American Music, February 9, 1964

Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Fatores influenciadores da gestão da qualidade e independência do auditor: um estudo de caso

Dissertação apresentada ao Instituto Superior de Contabilidade para obtenção do Grau de Mestre em Auditoria Orientada por: Doutora Alcina Dias

1969-70 Hockey Team

1969-71 Brock Generals Hockey team. Members from left to right - Back row: Tom Kearney (Trainer), Al Kellogg (Coach), John Hull, Craig Morrison, Gregg Law, Frank Mucci, Dale Andreas, Eric Stevens, Serge Girrard, John Clarey, Wayne Kenyon, Reg Egilsson, Dusty Papke, Randy Oiling (Manager). Front row: Ron Powel, Barry Hopkins, Bruce Wormald, Miller Hicks, Fred Carter, Mike Nicholson, Dick Overholt, Chris Shott. Missing: John O'Brien, Barry Elliot.

Maple Leaf Mills Records 1955, 1960-1964, 1975-1987, 1989, n.d.

Ontario Editorial Bureau (O.E.B.)

A. S. Whiting Manufacturing Company Limited, minute book, 1872-1909.

The Cedar Dale Scythe Works was the second manufacturing company that A.S. Whiting had established in Oshawa, the first being the Oshawa Manufacturing Co. in 1852. The Oshawa Manufacturing Co. was eventually taken over by the Joseph Hall Works in 1857. In 1862, the Cedar Dale Works was built after being in a rented space in the Hall Works for two years, building scythes and hoes. With the building of the firm, the village of Cedar Dale was established. In 1867, the firm became Whiting and Cowan when John Cowan bought into the company. After the death of Whiting in 1867, his son-in-law, R.S. Hamlin headed the company. By 1872, it became the A.S. Whiting Manufacturing Co. when Cowan withdrew from the business. Before Whiting’s death, the company had been profitable but due to new machinery being developed, hand tools were becoming obsolete and the business only lasted for a few more years (source: Oshawa Community Museum and Archives Web site).