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 approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% 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/beta-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.

Inference of the genetic architecture underlying BMI and height with the use of 20,240 sibling pairs

Evidence that complex traits are highly polygenic has been presented by population-based genome-wide association studies (GWASs) through the identification of many significant variants, as well as by family-based de novo sequencing studies indicating that several traits have a large mutational target size. Here, using a third study design, we show results consistent with extreme polygenicity for body mass index (BMI) and height. On a sample of 20,240 siblings (from 9,570 nuclear families), we used a within-family method to obtain narrow-sense heritability estimates of 0.42 (SE = 0.17, p = 0.01) and 0.69 (SE = 0.14, p = 6 x 10(-)(7)) for BMI and height, respectively, after adjusting for covariates. The genomic inflation factors from locus-specific linkage analysis were 1.69 (SE = 0.21, p = 0.04) for BMI and 2.18 (SE = 0.21, p = 2 x 10(-10)) for height. This inflation is free of confounding and congruent with polygenicity, consistent with observations of ever-increasing genomic-inflation factors from GWASs with large sample sizes, implying that those signals are due to true genetic signals across the genome rather than population stratification. We also demonstrate that the distribution of the observed test statistics is consistent with both rare and common variants underlying a polygenic architecture and that previous reports of linkage signals in complex traits are probably a consequence of polygenic architecture rather than the segregation of variants with large effects. The convergent empirical evidence from GWASs, de novo studies, and within-family segregation implies that family-based sequencing studies for complex traits require very large sample sizes because the effects of causal variants are small on average.

MPC controlled multirotor with suspended slung load: System architecture and visual load detection

There is an increased interest in the use of Unmanned Aerial Vehicles for load transportation from environmental remote sensing to construction and parcel delivery. One of the main challenges is accurate control of the load position and trajectory. This paper presents an assessment of real flight trials for the control of an autonomous multi-rotor with a suspended slung load using only visual feedback to determine the load position. This method uses an onboard camera to take advantage of a common visual marker detection algorithm to robustly detect the load location. The load position is calculated using an onboard processor, and transmitted over a wireless network to a ground station integrating MATLAB/SIMULINK and Robotic Operating System (ROS) and a Model Predictive Controller (MPC) to control both the load and the UAV. To evaluate the system performance, the position of the load determined by the visual detection system in real flight is compared with data received by a motion tracking system. The multi-rotor position tracking performance is also analyzed by conducting flight trials using perfect load position data and data obtained only from the visual system. Results show very accurate estimation of the load position (~5% Offset) using only the visual system and demonstrate that the need for an external motion tracking system is not needed for this task.

Observations on the Architecture of Evil: A New Reading of Eichmann on Kant

En route from Birmingham to Syria in 2013, British-Jihadi neophytes aged 22, Yusuf Sarwar and Mohammed Ahmed purchased two books via Amazon to prepare for their mission in Syria after joining ISIS: The Koran for Dummies and Islam for Dummies. Journalists were swift to disparage their reading. The book’s author, Princeton University campus imam, Sohaib Nazeer Sultan remarked “Even though they may have ordered it, I don't think they read it.” In 1933, aged 27, Adolf Eichmann moved to Berlin to join the Sicherheitsdienst SD whereupon he read Immanuel Kant’s book the Kritik der praktischen Vernunft (The Critique of Practical Reason) for the first time. After his trial in Jerusalem, Hannah Arendt of course dismissed Eichmann’s reading of the German philosopher as thoroughly vacuous. Ever since, writers have sought to undermine the veracity of Eichmann’s account. The global Jihadis are illiterate, a journalist recently commented: they’re not well read in the Qur’an, and if they have read it, they have thoroughly misunderstood it. He cited as evidence Abdul Raqib Amin’s YouTube rhetorical: Forget everyone. Read the Koran, read the instruction of life. Find out what is jihad. Eichmann on the other hand was not illiterate in his youth. Before Berlin, he had already read Kant’s Groundwork of the Metaphysics of Morals ; he would also re-read the Critique of Practical Reason, and from his testimony and terminology we can infer he was familiar with Kantian concepts that extend beyond both books...

The architecture of the psychiatric milieu

The last time a peer-reviewed volume on the future of mental health facilities was produced was in 1959, following a symposium organised by the American Psychological Association. The consensus was easy enough to follow and still resonates today: the best spaces to treat psychiatric illness will be in smaller, less restrictive units that offer more privacy and allow greater personalisation of space – possibly a converted hotel (Goshen, 1959). In some way, all those ideals have come to pass. An ideal typology was never established, but even so, units have shrunk from thousands of beds to units that typically house no more than 50 patients. Patients are generally more independent and are free to wander (within a unit) as they please. But the trend toward smaller and freer is reversing. This change is not driven by a desire to find the ideal building nor better models of care, but by growing concerns about budgets, self-harm and psychiatric violence. This issue of the Facilities comes at a time when the healthcare design is increasingly dominated by codes, statutes and guidelines. But the articles herein are a call to stop and think. We are not at the point where guidelines can be helpful, because they do not embody any depth of knowledge nor wisdom. These articles are intended to inject some new research on psychiatric/environmental interactions and also to remind planners and managers that guidelines might not tackle a core misunderstanding: fear-management about patient safety and the safety of society is not the purpose of the psychiatric facility. It is purpose is to create spaces that are suitable for improving the well-being of the mentally ill.

Are diverse factors proxies for architectural influences? A case for architecture in the aetiology of schizophrenia

Introduction The last half-century of epidemiological enquiry into schizophrenia can be characterized by the search for neurological imbalances and lesions for genetic factors. The growing consensus is that these directions have failed, and there is now a growing interest in psychosocial and developmental models. Another area of recent interest is in epigenetics – the multiplication of genetic influences by environmental factors. Methods This integrative review comparatively maps current psychosocial, developmental and epigenetic models for schizophrenia epidemiology to identify crossover and theoretical gaps. Results In the flood of data that is being produced around the schizophrenia epidemiology, one of the most consistent findings is that schizophrenia is an urban syndrome. Once demographic factors have been discounted, between one-quarter and one-third of all incidence is repeatedly traced back to urbanicity – potentially threatening more established models, such as the psychosocial, genetic and developmental hypotheses. Conclusions Close analysis demonstrates how current models for schizophrenia epidemiology appear to miss the mark. Furthermore, the built environment appears to be an inextricable factor in all current models and indeed may be a valid epidemiological factor on its own. The reason the built environment hasn’t already become a de rigueur area of epidemiological research is possibly trivial – it just doesn’t attract enough science, and lacks a hero to promote it alongside other hypotheses.

A hybrid agent architecture for modeling autonomous agents in SAGE

This paper highlights the Hybrid agent construction model being developed that allows the description and development of autonomous agents in SAGE (Scalable, fault Tolerant Agent Grooming Environment) - a second generation FIPA-Compliant Multi-Agent system. We aim to provide the programmer with a generic and well defined agent architecture enabling the development of sophisticated agents on SAGE, possessing the desired properties of autonomous agents - reactivity, pro-activity, social ability and knowledge based reasoning. © Springer-Verlag Berlin Heidelberg 2005.

Architecture designed ZnO hollow microspheres with wide-range visible-light photoresponses

It is a challenge to increase the visible-light photoresponses of wide-gap metal oxides. In this study, we proposed a new strategy to enhance the visible-light photoresponses of wide-gap semiconductors by deliberately designing a multi-scale nanostructure with controlled architecture. Hollow ZnO microspheres with constituent units in the shape of one-dimensional (1D) nanowire networks, 2D nanosheet stacks, and 3D mesoporous nanoball blocks are synthesized via an approach of two-step assembly, where the oligomers or the constituent nanostructures with specially designed structures are first formed, and then further assembled into complex morphologies. Through deliberate designing of constituent architectures allowing multiple visible-light scattering, reflections, and dispersion inside the multiscale nanostructures, enhanced wide range visible-light photoresponses of the ZnO hollow microspheres were successfully achieved. Compared to the one-step synthesized ZnO hollow microspheres, where no nanostructured constituents were produced, the ZnO hollow microspheres with 2D nanosheet stacks presented a 50 times higher photocurrent in the visible-light range (λ > 420 nm). The nanostructure induced visible-light photoresponse enhancement gives a direction to the development of novel photosensitive materials.

DIY/DIWO media architecture: The InstaBooth

Building on previous discourse regarding the ability of media architecture to be more open and accessible for the purposes of community engagement (Caldwell & Foth, 2014), this chapter explores a particular case study that was designed, constructed and implemented with the intention of allowing city users to participate in the development and creation of media architecture, the InstaBooth. In this chapter, we first explore DIY (do it yourself) and DIWO (do it with others) phenomena to examine what motivates the DIY cultures, communities, and practices. Secondly, in this chapter, we define and discuss our implementation of a DIY / DIWO media architecture example, the InstaBooth. The InstaBooth project pro-vides an opportunity to question the effectiveness of a DIY driven media architec-ture artefact to see to what extent it impacts on the experience of its users and for what benefit.

Scopophobia/Scopophilia: electric light and the anxiety of the gaze in postwar American architecture

In the years of reconstruction and economic boom that followed the Second World War, the domestic sphere encountered new expectations regarding social behaviour, modes of living, and forms of dwelling. This book brings together an international group of scholars from architecture, design, urban planning, and interior design to reappraise mid-twentieth century modern life, offering a timely reassessment of culture and the economic and political effects on civilian life. This collection contains essays that examine the material of art, objects, and spaces in the context of practices of dwelling over the long span of the postwar period. It asks what role material objects, interior spaces, and architecture played in quelling or fanning the anxieties of modernism’s ordinary denizens, and how this role informs their legacy today. Table of Contents [Book] Introduction Robin Schuldenfrei Part 1: Psychological Constructions: Anxiety of Isolation and Exposure 1. Taking Comfort in the Age of Anxiety: Eero Saarinen’s Womb Chair Cammie McAtee 2. The Future is Possibly Past: The Anxious Spaces of Gaetano Pesce Jane Pavitt 3. Scopophobia/Scopophilia: Electric Light and the Anxiety of the Gaze in American Postwar Domestic Architecture Margaret Petty Part 2: Ideological Objects: Design and Representation 4. The Allegory of the Socialist Lifestyle: The Czechoslovak Pavilion at the Brussels Expo, its Gold Medal and the Politburo Ana Miljacki 5. Assimilating Unease: Moholy-Nagy and the Wartime-Postwar Bauhaus in Chicago Robin Schuldenfrei 6. The Anxieties of Autonomy: Peter Eisenman from Cambridge to House VI Sean Keller Part 3: Societies of Consumers: Materialist Ideologies and Postwar Goods 7. "But a home is not a laboratory": The Anxieties of Designing for the Socialist Home in the German Democratic Republic 1950—1965 Katharina Pfützner 8. Architect-designed Interiors for a Culturally Progressive Upper-Middle Class: The Implicit Political Presence of Knoll International in Belgium Fredie Floré 9. Domestic Environment: Italian Neo-Avant-Garde Design and the Politics of Post-Materialism Mary Louise Lobsinger Part 4: Class Concerns and Conflict: Dwelling and Politics 10. Dirt and Disorder: Taste and Anxiety in the Working Class Home Christine Atha 11. Upper West Side Stories: Race, Liberalism, and Narratives of Urban Renewal in Postwar New York Jennifer Hock 12. Pawns or Prophets? Postwar Architects and Utopian Designs for Southern Italy Anne Parmly Toxey. Coda: From Homelessness to Homelessness David Crowley

Heritability of the network architecture of intrinsic brain functional connectivity

The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23±2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h2 (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤15%), and when global signal regression was implemented, heritability estimates decreased substantially h2 (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.

Blurring the physical boundaries of the city: Media architecture and urban informatics for community engagement

Architecture focuses on designing built environments in response to society’s needs, reflecting culture through materials and forms. The physical boundaries of the city have become blurred through the integration of digital media, connecting the physical environment with the digital. In the recent past the future was imagined as highly technological; 1982 Ridley Scott’s Blade Runner is set in 2019 and introduces a world where supersized screens inject advertisements in the cluttered urban space. Now, in 2015 screens are central to everyday life, but in a completely different way in respect to what had been imagined. Through ubiquitous computing and social media, information is abundant. Digital technologies have changed the way people relate to cities supporting discussion on multiple levels, allowing citizens to be more vocal than ever before. We question how architects can use the affordances of urban informatics to obtain and navigate useful social information to inform design. This chapter investigates different approaches to engage communities in the debate on cities, in particular it aims to capture citizens’ opinions on the use and design of public places. Physical and digital discussions have been initiated to capture citizens’ opinions on the use and design of public places. In addition to traditional consultation methods, Web 2.0 platforms, urban screens, and mobile apps are used in the context of Brisbane, Australia to explore contemporary strategies of engagement (Gray 2014).