Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Review of Richard Friedli & Mallory Schneuwly Purdie (eds), L’Europe des Religions. Éléments d’analyse des champs religieux européens. Actes du programme 2002-2003 de formation doctorale.

Book Review in Schweizerische Zeitschrift für Religions und Kulturgeschichte No. 100 (2006) of Richard Friedli & Mallory Schneuwly Purdie (eds), L’Europe des Religions. Éléments d’analyse des champs religieux européens. Actes du programme 2002-2003 de formation doctorale, Berne: Peter Lang, collection « Studia Religiosa Helvetica », vol.8/9, 2004, 257p.

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.

Opening truth to imagination : the pragmatism of John Dewey and Richard Rorty

This study explores in a comparative way the works of two American pragmatist philosophers-John Dewey and Richard Rorty. I have provided a reading of their broader works in order to offer what I hope is a successful sympathetic comparison where very few exist. Dewey is often viewed as the central hero in the classical American pragmatic tradition, while Rorty, a contemporary pragmatist, is viewed as some sort of postmodern villain. I show that the different approaches by the two philosophers-Dewey's experiential focus versus Rorty's linguistic focus-exist along a common pragmatic continuum, and that much of the critical scholarship that pits the two pragmatists against each other has actually created an unwarranted dualism between experience and language. I accomplish this task by following the critical movement by each of the pragmatists through their respective reworking of traditional absolutist truth conceptions toward a more aesthetical, imaginative position. I also show how this shift or "turning" represents an important aspect of the American philosophical tradition-its aesthetic axis. I finally indicate a role for liberal education (focusing on higher nonvocational education) in accommodating this turning, a turning that in the end is necessitated by democracy's future trajectory

The Clemente Course in the Humanities and critical pedagogy : a comparative analysis of Earl Shorris and bell hooks on poverty, racism, imperialism and patriarchy

The Clemente Course in the Humanities is an anti-poverty intervention for adults who self-identity as "poor" and humanities instructors. The course was created in 1995 by journalist Earl Shorris, who based the curriculum on a Socratic method of pedagogy and the "great books" canon of Robert Hutchins. It began as a community-based initiative in urban US settings, but since 1997 Mayan, Yup'ik and Cherokee iterations have been created, as well as on-campus bridge courses for non-traditional students to explore college-level education in Canada and the USA. The course potentially conflicts with critical pedagogy because the critical theories of Paulo Freire and contemporary cultural studies reject traditional notions of both the canon and teaching. However, a comparison between Shorris' and bell hooks' theories of oppression reveals significant similarities between his "surround of force" and her "capitalist imperialist white supremacist patriarchy," with implications for liberal studies and critical pedagogy.

Photograph of Richard, Iris and Albert Sloman [n.d.]

An undated photograph of Richard, Iris and Albert Sloman taken outside what is believed to be a holiday cabin in Parry Sound, Ontario. This photograph was in the possession of the Rick Bell family, of St. Catharines.

Indenture of Land Sold by David Secord to George Shaw, Richard Woodruff, Timothy Street, Josiah Brown, Henry Pope

Indenture regarding land sold by David Secord of St. Davids to George Shaw, Richard Woodruff, Timothy Street and Josiah Brown, all of Niagara Township and Reverend Henry Pope of York. The land includes part of Lot no. 90 in the Township of Niagara. September 5, 1820.

Indenture Lease of Land by David Secord to Richard and William Woodruff

Indenture stating that David Secord of the Township of Niagara leased the dam of the sawmill pond in St. Davids to Richard and William Woodruff for 25 shillings per year for their mill business, May 2, 1824.

Indenture of Land Sold by George Shaw to Richard and William Woodruff

Indenture stating that George Shaw of Niagara sold 1 acre, 2 roods and 1 perch in the Village of St. Davids to Richard and William Woodruff. The price was 66 pounds - instrument no. 6926, June 9, 1824.

Indenture of Conveyance between George Shaw and Richard Woodruff and Company

Indenture of conveyance between George Shaw of the Township of Niagara and Richard Woodruff and Company, merchants of the Township of Niagara, all living in the Village of St. Davids for a share of water ("course of water running in a hole one inch diameter"), April 15, 1825.

List of prices paid to Dr. Richard King from Dilly Coleman

List of prices paid to Dr. Richard King from Dilly Coleman in regard to items such as flour and a live hog which were sold to Dr. King by Mr. Coleman and medical treatment and medicines for Dilly and his family provided by Dr. King. Samuel Woodruff’s name appears on the outside of this list, n.d.