Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology

Aliens versus Humans: Do avatars make a difference in how we play the game?

An immersive first-person 3D computer game was designed and developed to investigate if the visual characteristics of a player's avatar influences their behavior. Two types of gender-matched biped avatar were used: Normal looking Humanoids and tougher looking Aliens. In the game, players had to block incoming projectiles fired from two canons with their hands. The number of times the players were hit as well as a measure of how hard they hit the projectiles was recorded. Results show differences in these measures dependent on the type of avatar used, in line with previous findings whereby people appear to be influenced by the perceived characteristics of their digital representation

Aliens versus Humans: Do avatars make a difference in how we play the game?

An immersive first-person 3D computer game was designed and developed to investigate if the visual characteristics of a player's avatar influences their behavior. Two types of gender-matched biped avatar were used: Normal looking Humanoids and tougher looking Aliens. In the game, players had to block incoming projectiles fired from two canons with their hands. The number of times the players were hit as well as a measure of how hard they hit the projectiles was recorded. Results show differences in these measures dependent on the type of avatar used, in line with previous findings whereby people appear to be influenced by the perceived characteristics of their digital representation

Virtual Buzzwire: assessment of a prototype VR game for stroke rehabilitation

We created a VR version of the Buzzwire children’s toy as part of a project to develop tools for assessment and rehabilitation of upper-body motor skills for people with dexterity impairment after stroke. In two pilot studies, participants wearing a HMD used a hand-held wand with precision tracking to traverse virtual ‘wires’. In the first study, we compared able-bodied participant’s performance with and without binocular viewing to establish a connection with previous experiments using physical versions of the game. Furthermore, we show that our extended measures were could also discern differences between subjects’ dominant versus non-dominant hand. In a second study, we assessed the usability of the system on a small sample of subjects with post-stroke hemiparesis. There was positive acceptance of the technology with no fatigue or nausea and measurements highlighted the differences between the hemiparetic and unaffected hand

BuzzwireVR: An Immersive Game to Supplement Fine-Motor Movement Therapy

Recovery of upper-body fine-motor skills after brain trauma, e.g. after a stroke, involves a long process of movement rehabilitation. When the arms and hands are affected patients often spend many hours exercising in order to regain control of their movements, often using children's toys. This paper describes the process of development of a Virtual Reality (VR) system designed to supplement rehabilitation by encouraging hand movements while playing a fun game. The system is based on the well-known Buzzwire children's toy that requires steady hand-eye coordination to pass a ring along a wire without touching the wire. The toy has in the past been used in a variety of research studies, but we considered it ideal for motor rehabilitation because it requires steady hand and finger movements. In our virtualised version of the toy the wire consists of a parametric spline curve with cylindrical cross-section positioned in front of the player. Cylinders at the ends of the 'wire' change colour to indicate which hand to use. The parametric nature of the wire allows us to record performance variables which are not readily available in the physical version. We report on two initial experiments which tested and evaluated various aspects of performance on able-bodied participants and stroke patients, followed by a description of how we developed the toy into a multi-level game that encourages increasingly intricate hand movements. In the first evaluation we tested if performance variables (such as average speed, and distance from the wire) could distinguish between dominant and non-dominant hands of able-bodied participants. We also compared performance with and without binocular viewing. Results showed that our metrics could distinguish between the players dominant versus non-dominant hand. We also noted a dramatic disruption of performance when binocular stereopsis was not available. The second experiment was a usability study involving a sample of stroke-affected participants with post-stroke hemiparesis. Results showed positive acceptance of the technology with no fatigue or nausea. Our gamified version of the task utilizes learnings from the previous studies to create an enjoyable multi-level game involving auditory guidance as feedback. Results are discussed in terms of potential benefits of using such technology in addition to conventional therapy

A virtual reality loop and wire game for stroke rehabilitation

This paper describes the process of development of a Virtual Reality (VR) system which encourages people to exercise and improve their upper-body motor skills after stroke. The system is based on the Buzzwire children’s toy, the physical version of which involves traversing a wire using a loop and wand that closes a circuit and makes a sound when the loop touches the wire. In our VR version users wearing a HMD and holding a tracked wand attempt to traverse a virtual ‘wire’. The ‘wire’ is based on a parametric spline curve and allows us to measure more performance variables than the physical version of the game. The paper describes the initial 2 experiments which test and evaluate aspects of performance, followed by a description of a prototype version of the game. In the first evaluation we tested if performance variables (such as average speed, and distance from the wire) could distinguish between dominant and non-dominant hands of able-bodied subjects. We also compared binocular with monocular viewing. Results showed benefits for dominant over non-dominant hand-control and a dramatic reduction in performance when binocular stereopsis is absent. The second experiment was a usability study involving a sample of stroke affected patients with hemiparesis. Results showed positive acceptance of the technology with no fatigue or nausea and some significant differences between affected and unaffected hand control. Our prototype utilizes learnings from the previous studies to create an enjoyable multi-level version of the game involving auditory guidance as feedback. However, we still require some measure of efficiency of movement by which we can assess kinematic improvements over time

Weak Governments and Trade Agreements *

Abstract The recent theoretical literature on the determinants of trade agreements has stressed the importance of political gains, such as credibility, as a rationale for trade agreements. The empirical literature, however, has lagged behind in the estimation of the economic gains or losses associated with these politically motivated trade agreements. This paper fills that gap by providing estimates of the economic impact of politically and economically motivated trade agreements. We find that credibility gains play a role in increasing the probability of two countries signing an agreement. Moreover, agreements with a stronger political motivation are more trade creating than agreements that are signed for pure market access / economic reasons. JEL classification numbers: F13, F15, D72