166 resultados para Newman, Harry


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There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

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Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

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In this paper, we analyse a block cipher mode of operation submitted in 2014 to the cryptographic competition for authenticated encryption (CAESAR). This mode is designed by Recacha and called ++AE (plus-plus-ae). We propose a chosen plaintext forgery attack on ++AE that requires only a single chosen message query to allow an attacker to construct multiple forged messages. Our attack is deterministic and guaranteed to pass ++AE integrity check. We demonstrate the forgery attack using 128-bit AES as the underlying block cipher. Hence, ++AE is insecure as an authenticated encryption mode of operation.

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This paper seeks to draw attention to the importance of appreciating and using ever-present diversity to achieve increased legitimacy for entrepreneurship education. As such, it aims to draw the reader into a reflective process of discovery as to why entrepreneurship education is important and how such importance can be prolonged. Design/methodology/approach - The paper revisits Gartner's 1985 conceptual framework for understanding the complexity of entrepreneurship. The paper proposes an alternative framework based on the logic of Gartner's framework to advance the understanding of entrepreneurship education. The authors discuss the dimensions of the proposed framework and explain the nature of the dialogic relations contained within. Findings - It is argued that the proposed conceptual framework provides a new way to understand ever-present heterogeneity related to the development and delivery of entrepreneurship education. Practical implications - The paper extends an invitation to the reader to audit their own involvement and proximity to entrepreneurship education. It argues that increased awareness of the value that heterogeneity plays in student learning outcomes and programme branding is directly related to the presence of heterogeneity across the dimensions of the conceptual framework. Originality/value - The paper introduces a simple yet powerlu1 means of understanding what factors contribute to the success or otherwise of developing and delivering entrepreneurship education. The simplicity of the approach suggested provides all entrepreneurship educators with the means to audit all facets of their programme.

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Purpose The purpose of this paper is to highlight the importance of enterprise educators working collectively to develop a unique scholarship of teaching. The authors argue that the time is right for educators in this domain to secure the future of enterprise education. Acknowledging the debate between "entrepreneurship education" and "enterprise education," the authors set out to develop a unification model through which educators can act collectively to demonstrate the leadership required to secure the autonomy of the domain. Design/methodology/approach The authors bring several pertinent ideas (pedagogical content knowledge, heutagogy and academagogy) to the attention of academics/researchers involved in the design, development and delivery of enterprise education. The innovative approach to combine these ideas with prevailing thinking in this domain has facilitated a model for collective action. Findings It is at the level of the shared philosophical positions that the authors can best cooperate to shape the future direction of enterprise education. The authors argue against dwelling upon how the authors differ in terms of context and process issues. Such matters can only fragment the theory and practice of enterprise education. The authors need to develop greater appreciation of shared philosophical positions and leverage this understanding into a unique scholarship of teaching, specific to enterprise education. Practical implications – As enterprise education becomes more global, it is also likely to become more attractive to business schools that long for a new positioning tool in the increasingly overcrowded markets that they compete in. Originality/value This paper encourages enterprise educators to reflect upon the knowledge they hold of their own practice, and that of other enterprise educators.

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It has been noted elsewhere that an idea is acknowledged to be creative if it is novel, or surprising and adaptive. So how does that fit with education's desire to measure student performance against fixed, consistent and predicted learning outcomes? This study explores practical measures and theoretical constructs that address the dearth of teaching, learning and assessment strategies to enhance creative capacity in enterprise and entrepreneurship education. It is argued that inappropriate assessment strategies can be significant inhibitors of the creativity of students and teachers. Referring to the broader discipline of 'design', as defined by Bruce and Besant (2002) – the application of human creativity to a purpose – both broad employer satisfaction with education and fast growing economic success are found (DCMS, 2014). As predictable assessment outcomes equal predictable students, these understandings can inform educators who wish to map and develop enhanced creative endeavours such as opportunity recognition, communication and innovation.

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This article offers a critical discussion of the role of the business plan in current enterprise educational practice. In addition to reviewing recent work that considers the ‘for’ and ‘against’ arguments about the use of business plans in higher education, the authors suggest that the context of student learning is largely omitted from these discussions. As such, they contextualize the debate so that the purpose of the business plan can be better appreciated. They build on recent work that offers alternatives to the business plan – approaches directly focused on customer discovery and explicit testing of assumptions. In doing so, recent concerns about the value of business plans and, conversely, the views of those who argue in favour of the role of business plans in enterprise education, are noted. The article provides insights into emerging alternative practices in the field of enterprise education, practices based on students’ use of such education as a vehicle for skills and knowledge development and/or wealth creation. It is acknowledged that various biases are present in the current debate, including those of the present authors: whilst it is accepted that these biases are unlikely to disappear, the article contextualizes their origins.

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Purpose The purpose of this paper is to provocatively enter four imagined worlds of enterprise education with the express aim of contemplating an emerging future. The authors do so not to expressly determine what positioning is most appropriate for enterprise/entrepreneurship education, but rather to consider the issues associated with each of the four imagined worlds. Design/methodology/approach The authors’ approach is built around a combination of cycles of reflective practice and the use of scenario development processes. The authors seek to suspend their collective judgement whilst entering the four imagined worlds, but ultimately do not claim to have hidden their personal biases. Findings It is concluded that enterprise/entrepreneurship education should be shared across the university and not owned by any school or faculty. While the authors find it difficult to dismiss the underlying purpose of each scenario, they sense an opportunity to unite their common focus on the development of a transformative student experience. Practical implications This process has provided unexpected insights into the potential of scenario planning as a tool that could conceivably be employed more often to tackle complex issues, such as the positioning of enterprise/entrepreneurship education in Higher Education. Originality/value This paper, despite its inherent biases, offers the reader an opportunity to gain a sense of the various roles forced upon enterprise/entrepreneurship education by its various key stakeholders. In doing so, the shortcomings of the current situation are highlighted.

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In just one of the many extraordinary moments during the spectacular Opening Ceremony of the 2012 London Olympic Games, thirty Mary Poppinses floated into the stadium on their umbrellas to battle a 40 foot-long inflatable Lord Voldemort. This multi-million pound extravaganza was telecast to a global audience of over one billion people, highlighting in an extremely effective manner the grandeur and eccentricities of the host nation, and featuring uniquely British icons such as Mr Bean, James Bond, The Beatles and Harry Potter, as well as those quintessential icons of Englishness, the Royal Family, double-decker red buses and the National Health Service.

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There has been much controversy over the Trans-Pacific Partnership (TPP) – a plurilateral trade agreement involving a dozen nations from throughout the Pacific Rim – and its impact upon the environment, biodiversity, and climate change. The secretive treaty negotiations involve Australia and New Zealand; countries from South East Asia such as Brunei Darussalam, Malaysia, Singapore, Vietnam, and Japan; the South American nations of Peru and Chile; and the members of the 1994 North American Free Trade Agreement (NAFTA), Canada, Mexico and the United States. There was an agreement reached between the parties in October 2015. The participants asserted: ‘We expect this historic agreement to promote economic growth, support higher-paying jobs; enhance innovation, productivity and competitiveness; raise living standards; reduce poverty in our countries; and to promote transparency, good governance, and strong labor and environmental protections.’ The final texts of the agreement were published in November 2015. There has been discussion as to whether other countries – such as Indonesia, the Philippines, and South Korea – will join the deal. There has been much debate about the impact of this proposed treaty upon intellectual property, the environment, biodiversity and climate change. There have been similar concerns about the Trans-Atlantic Trade and Investment Partnership (TTIP) – a proposed trade agreement between the United States and the European Union. In 2011, the United States Trade Representative developed a Green Paper on trade, conservation, and the environment in the context of the TPP. In its rhetoric, the United States Trade Representative has maintained that it has been pushing for strong, enforceable environmental standards in the TPP. In a key statement in 2014, the United States Trade Representative Mike Froman insisted: ‘The United States’ position on the environment in the Trans-Pacific Partnership negotiations is this: environmental stewardship is a core American value, and we will insist on a robust, fully enforceable environment chapter in the TPP or we will not come to agreement.’ The United States Trade Representative maintained: ‘Our proposals in the TPP are centered around the enforcement of environmental laws, including those implementing multilateral environmental agreements (MEAs) in TPP partner countries, and also around trailblazing, first-ever conservation proposals that will raise standards across the region’. Moreover, the United States Trade Representative asserted: ‘Furthermore, our proposals would enhance international cooperation and create new opportunities for public participation in environmental governance and enforcement.’ The United States Trade Representative has provided this public outline of the Environment Chapter of the TPP: A meaningful outcome on environment will ensure that the agreement appropriately addresses important trade and environment challenges and enhances the mutual supportiveness of trade and environment. The Trans-Pacific Partnership countries share the view that the environment text should include effective provisions on trade-related issues that would help to reinforce environmental protection and are discussing an effective institutional arrangement to oversee implementation and a specific cooperation framework for addressing capacity building needs. They also are discussing proposals on new issues, such as marine fisheries and other conservation issues, biodiversity, invasive alien species, climate change, and environmental goods and services. Mark Linscott, an assistant Trade Representative testified: ‘An environment chapter in the TPP should strengthen country commitments to enforce their environmental laws and regulations, including in areas related to ocean and fisheries governance, through the effective enforcement obligation subject to dispute settlement.’ Inside US Trade has commented: ‘While not initially expected to be among the most difficult areas, the environment chapter has emerged as a formidable challenge, partly due to disagreement over the United States proposal to make environmental obligations binding under the TPP dispute settlement mechanism’. Joshua Meltzer from the Brookings Institute contended that the trade agreement could be a boon for the protection of the environment in the Pacific Rim: Whether it is depleting fisheries, declining biodiversity or reduced space in the atmosphere for Greenhouse Gas emissions, the underlying issue is resource scarcity. And in a world where an additional 3 billion people are expected to enter the middle class over the next 15 years, countries need to find new and creative ways to cooperate in order to satisfy the legitimate needs of their population for growth and opportunity while using resources in a manner that is sustainable for current and future generations. The TPP parties already represent a diverse range of developed and developing countries. Should the TPP become a free trade agreement of the Asia-Pacific region, it will include the main developed and developing countries and will be a strong basis for building a global consensus on these trade and environmental issues. The TPP has been promoted by its proponents as a boon to the environment. The United States Trade Representative has maintained that the TPP will protect the environment: ‘The United States’ position on the environment in the TPP negotiations is this: environmental stewardship is a core American value, and we will insist on a robust, fully enforceable environment chapter in the TPP or we will not come to agreement.’ The United States Trade Representative discussed ‘Trade for a Greener World’ on World Environment Day. Andrew Robb, at the time the Australian Trade and Investment Minister, vowed that the TPP will contain safeguards for the protection of the environment. In November 2015, after the release of the TPP text, Rohan Patel, the Special Assistant to the President and Deputy Director of Intergovernmental Affairs, sought to defend the environmental credentials of the TPP. He contended that the deal had been supported by the Nature Conservancy, the International Fund for Animal Welfare, the Joint Ocean Commission Initiative, the World Wildlife Fund, and World Animal Protection. The United States Congress, though, has been conflicted by the United States Trade Representative’s arguments about the TPP and the environment. In 2012, members of the United States Congress - including Senator Ron Wyden (D-OR), Olympia Snowe (R-ME), and John Kerry (D-MA) – wrote a letter, arguing that the trade agreement needs to provide strong protection for the environment: ‘We believe that a '21st century agreement' must have an environment chapter that guarantees ongoing sustainable trade and creates jobs, and this is what American businesses and consumers want and expect also.’ The group stressed that ‘A binding and enforceable TPP environment chapter that stands up for American interests is critical to our support of the TPP’. The Congressional leaders maintained: ‘We believe the 2007 bipartisan congressional consensus on environmental provisions included in recent trade agreements should serve as the framework for the environment chapter of the TPP.’ In 2013, senior members of the Democratic leadership expressed their opposition to granting President Barack Obama a fast-track authority in respect of the TPP House of Representatives Minority Leader Nancy Pelosi said: ‘No on fast-track – Camp-Baucus – out of the question.’ Senator Majority leader Harry Reid commented: ‘I’m against Fast-Track: Everyone would be well-advised to push this right now.’ Senator Elizabeth Warren has been particularly critical of the process and the substance of the negotiations in the TPP: From what I hear, Wall Street, pharmaceuticals, telecom, big polluters and outsourcers are all salivating at the chance to rig the deal in the upcoming trade talks. So the question is, Why are the trade talks secret? You’ll love this answer. Boy, the things you learn on Capitol Hill. I actually have had supporters of the deal say to me ‘They have to be secret, because if the American people knew what was actually in them, they would be opposed. Think about that. Real people, people whose jobs are at stake, small-business owners who don’t want to compete with overseas companies that dump their waste in rivers and hire workers for a dollar a day—those people, people without an army of lobbyists—they would be opposed. I believe if people across this country would be opposed to a particular trade agreement, then maybe that trade agreement should not happen. The Finance Committee in the United States Congress deliberated over the Trans-Pacific Partnership negotiations in 2014. The new chair Ron Wyden has argued that there needs to be greater transparency in trade. Nonetheless, he has mooted the possibility of a ‘smart-track’ to reconcile the competing demands of the Obama Administration, and United States Congress. Wyden insisted: ‘The new breed of trade challenges spawned over the last generation must be addressed in imaginative new policies and locked into enforceable, ambitious, job-generating trade agreements.’ He emphasized that such agreements ‘must reflect the need for a free and open Internet, strong labor rights and environmental protections.’ Elder Democrat Sander Levin warned that the TPP failed to provide proper protection for the environment: The TPP parties are considering a different structure to protect the environment than the one adopted in the May 10 Agreement, which directly incorporated seven multilateral environmental agreements into the text of past trade agreements. While the form is less important than the substance, the TPP must provide an overall level of environmental protection that upholds and builds upon the May 10 standard, including fully enforceable obligations. But many of our trading partners are actively seeking to weaken the text to the point of falling short of that standard, including on key issues like conservation. Nonetheless, 2015, President Barack Obama was able to secure the overall support of the United States Congress for his ‘fast-track’ authority. This was made possible by the Republicans and dissident Democrats. Notably, Oregon Senator Ron Wyden switched sides, and was transformed from a critic of the TPP to an apologist for the TPP. For their part, green political parties and civil society organisations have been concerned about the secretive nature of the negotiations; and the substantive implications of the treaty for the environment. Environmental groups and climate advocates have been sceptical of the environmental claims made by the White House for the TPP. The Green Party of Aotearoa New Zealand, the Australian Greens and the Green Party of Canada have released a joint declaration on the TPP observing: ‘More than just another trade agreement, the TPP provisions could hinder access to safe, affordable medicines, weaken local content rules for media, stifle high-tech innovation, and even restrict the ability of future governments to legislate for the good of public health and the environment’. In the United States, civil society groups such as the Sierra Club, Public Citizen, WWF, the Friends of the Earth, the Rainforest Action Network and 350.org have raised concerns about the TPP and the environment. Allison Chin, President of the Sierra Club, complained about the lack of transparency, due process, and public participation in the TPP talks: ‘This is a stealth affront to the principles of our democracy.’ Maude Barlow’s The Council of Canadians has also been concerned about the TPP and environmental justice. New Zealand Sustainability Council executive director Simon Terry said the agreement showed ‘minimal real gains for nature’. A number of organisations have joined a grand coalition of civil society organisations, which are opposed to the grant of a fast-track. On the 15th January 2013, WikiLeaks released the draft Environment Chapter of the TPP - along with a report by the Chairs of the Environmental Working Group. Julian Assange, WikiLeaks' publisher, stated: ‘Today's WikiLeaks release shows that the public sweetener in the TPP is just media sugar water.’ He observed: ‘The fabled TPP environmental chapter turns out to be a toothless public relations exercise with no enforcement mechanism.’ This article provides a critical examination of the draft Environment Chapter of the TPP. The overall argument of the article is that the Environment Chapter of the TPP is an exercise in greenwashing – it is a public relations exercise by the United States Trade Representative, rather than a substantive regime for the protection of the environment in the Pacific Rim. Greenwashing has long been a problem in commerce, in which companies making misleading and deceptive claims about the environment. In his 2012 book, Greenwash: Big Brands and Carbon Scams, Guy Pearse considers the rise of green marketing and greenwashing. Government greenwashing is also a significant issue. In his book Storms of My Grandchildren, the climate scientist James Hansen raises his concerns about government greenwashing. Such a problem is apparent with the TPP – in which there was a gap between the assertions of the United States Government, and the reality of the agreement. This article contends that the TPP fails to meet the expectations created by President Barack Obama, the White House, and the United States Trade Representative about the environmental value of the agreement. First, this piece considers the relationship of the TPP to multilateral environmental treaties. Second, it explores whether the provisions in respect of the environment are enforceable. Third, this article examines the treatment of trade and biodiversity in the TPP. Fourth, this study considers the question of marine capture fisheries. Fifth, there is an evaluation of the cursory text in the TPP on conservation. Sixth, the article considers trade in environmental services under the TPP. Seventh, this article highlights the tensions between the TPP and substantive international climate action. It is submitted that the TPP undermines effective and meaningful government action and regulation in respect of climate change. The conclusion also highlights that a number of other chapters of the TPP will impact upon the protection of the environment – including the Investment Chapter, the Intellectual Property Chapter, the Technical Barriers to Trade Chapter, and the text on public procurement.

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An application that translates raw thermal melt curve data into more easily assimilated knowledge is described. This program, called ‘Meltdown’, performs a number of data remediation steps before classifying melt curves and estimating melting temperatures. The final output is a report that summarizes the results of a differential scanning fluorimetry experiment. Meltdown uses a Bayesian classification scheme, enabling reproducible identification of various trends commonly found in DSF datasets. The goal of Meltdown is not to replace human analysis of the raw data, but to provide a sensible interpretation of the data to make this useful experimental technique accessible to naïve users, as well as providing a starting point for detailed analyses by more experienced users.

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It is a transforming experience to imagine that in 50 years, our current built environment might look as foreign to our grandchildren as the computers of the 1960s look to us today. We can already see emerging attempts to create cities that are resilient and liveable in the face of physical stresses including population growth, increasing climate variability, resource shortages and pollution. The capacity for transforming every aspect of development towards resilience and liveability goals is profoundly exciting, from heating and cooling through to energy generation, water reticulation, food production, transportation, communication and recreational spaces...

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Background Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. Methods/Design This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 − 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. Discussion The trial will provide evidence for the safety and effectiveness of watchful waiting for the management of AOM in Aboriginal and Torres Strait Islander children living in urban settings who are considered to be at low risk of complications.

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Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

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A promotional brochure celebrating the completion of the Seagram Building in spring 1957 features on its cover intense portraits of seven men bisected by a single line of bold text that asks, “Who are these Men?” The answer appears on the next page: “They Dreamed of a Tower of Light” (Figures 1, 2). Each photograph is reproduced with the respective man’s name and project credit: architects, Mies van der Rohe and Philip Johnson; associate architect, Eli Jacques Kahn; electrical contractor, Harry F. Fischbach; lighting consultant, Richard Kelly; and electrical engineer, Clifton E. Smith. To the right, a rendering of the new Seagram Tower anchors the composition, standing luminous against a star-speckled night sky; its glass walls and bronze mullions are transformed into a gossamer skin that reveals the tower’s structural skeleton. Lightolier, the contract lighting manufacturer, produced the brochure to promote its role in the lighting of the Seagram Building, but Lightolier’s promotional copy was not far from the truth.