Freedom and constraint analysis and optimization

Many mathematical and intuitive methods for constraint analysis of mechanisms have been proposed. In this article we compare three methods. Method one is based on Grüblers equation. Method two uses an intuitive analysis method based on opening kinematic loops and evaluating the constraints at the intersection. Method three uses a flexible multibody modeling approach which facilitates the analysis of complex systems. We demonstrate a visualization method using generalized von Mises stress to show overconstraint modes. A four bar mechanism and a two-degree-of- freedom (DOF) flexure-based mechanism serve as a case study. Briefly the optimization of the location and orientation of releases is discussed. The implementation of the releases in the flexure-based two DOF mechanism is presented.\u

A two-node superelement description for modelling of flexible complex-shared beam-like components

In this paper, a two-node superelement description is proposed for use in multibody models which is capable of modelling flexible complex-shaped beam-like components. Assuming that the deformations with respect to a co-rotational frame remain small, substructuring methods may be used to obtain a dynamical model with reduced mass and stiffness matrices from a linear finite element model. The development of a two-node superelement is established by linking a reduced linear finite element model with a non-linear finite beam element capable of describing large rigid body motion and small elastic deformations. This is achieved by equating their potential and kinetic energies. Two examples are included. A simulation of the spin-up motion of a flexible beam with uniform cross-section and a similar simulation in which the beam is simultaneously excited in the out-of-plane direction. Both examples show good\ud agreement with simulations obtained using non-linear finite beam elements

On the order of a non-abelian representation group of a slim dense near hexagon

We show that, if the representation group $R$ of a slim dense near hexagon $S$ is non-abelian, then $R$ is of exponent 4 and $|R|=2^{\beta}$, $1+NPdim(S)\leq \beta\leq 1+dimV(S)$, where $NPdim(S)$ is the near polygon embedding dimension of $S$ and $dimV(S)$ is the dimension of the universal representation module $V(S)$ of $S$. Further, if $\beta =1+NPdim(S)$, then $R$ is an extraspecial 2-group (Theorem 1.6)

Geometric Hyperplanes of the Near Hexagon L_3 times GQ(2, 2)

Having in mind their potential quantum physical applications, we classify all geometric hyperplanes of the near hexagon that is a direct product of a line of size three and the generalized quadrangle of order two. There are eight different kinds of them, totalling to 1023 = 2^{10} - 1 = |PG(9, 2)|, and they form two distinct families intricately related with the points and lines of the Veldkamp space of the quadrangle in question.Comment: 10 pages, 5 figures and 2 tables; Version 2 - more detailed discussion of the properties of hyperplane

For which clinical rules do doctors want decision support, and why? A survey of Dutch general practitioners.

Despite the promise of decision support for improving care, alerts are often overridden or ignored. We evaluated Dutch general practitioners’ intention to accept decision support in a proposed implementation based on clinical rules regarding care for elderly patients, and their reasons for wanting or not wanting support. We developed a survey based on literature and structured interviews and distributed it to all doctors who would receive support in the proposed implementation (n = 43), of which 65 percent responded. The survey consisted of six questions for each of 20 clinical rules. Despite concerns about interruption, doctors tended to choose more interruptive forms of support. Doctors wanted support when they felt the rule represented minimal care, perceived a need to improve care, and felt responsible for the action and that they might forget to perform the action; doctors declined support due to feeling that it was unnecessary and due to concerns about interruption

Outcome Measures of New Technologies in Uveal Melanoma Review from the European Vision Institute Special Interest Focus Group Meeting

Uveal melanoma UM is the most common primary intraocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute EVI special interest focus group was held on Outcome Measures of New Technologies in Uveal Melanoma, addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient s well being. This review highlights the meeting s presentations in the context of the published literatur

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function