An Integrated Engineering Model for Advising

This evidence-based practice paper describes the theoretical foundations of the supportive advising practices used by the Integrated Engineering Department (IE) at Minnesota State University, Mankato. The driving motivation for the advising model is to support the development of student engineers as whole people. Generally in academia, faculty in traditional professor roles serve as formal advisors, mentors, facilitators, evaluators, and coaches and are joined by full-time staff that serve in roles to support student development. Integrated Engineers at Minnesota State University, Mankato are supported to become the engineer they want to be. This paper describes the unique model employed by IE of mentoring and advising that incorporates not just faculty but staff, industry mentors or facilitators, and peers that bring different perspectives to student support. Evidence of effectiveness includes high graduation rates, career placement rates of students, and student perceptions of preparation for meeting our program educational objectives. Perspectives from faculty new to the program and current and former students illustrate the personal impact of the model

Genome-wide association study of proneness to anger

BACKGROUND: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. METHODS: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,747). RESULTS: Subjects were, on average, 54 (range 45-64) years old at baseline enrollment, 47% (n = 4,117) were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 +/- 1.8 and 7.6 +/- 2.2. We observed a nominally significant finding (p = 2.9E-08, lambda = 1.027 - corrected pgc = 2.2E-07, lambda = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. CONCLUSIONS: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3)-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament

Non-existence and uniqueness results for supercritical semilinear elliptic equations

Non-existence and uniqueness results are proved for several local and non-local supercritical bifurcation problems involving a semilinear elliptic equation depending on a parameter. The domain is star-shaped but no other symmetry assumption is required. Uniqueness holds when the bifurcation parameter is in a certain range. Our approach can be seen, in some cases, as an extension of non-existence results for non-trivial solutions. It is based on Rellich-Pohozaev type estimates. Semilinear elliptic equations naturally arise in many applications, for instance in astrophysics, hydrodynamics or thermodynamics. We simplify the proof of earlier results by K. Schmitt and R. Schaaf in the so-called local multiplicative case, extend them to the case of a non-local dependence on the bifurcation parameter and to the additive case, both in local and non-local settings.Comment: Annales Henri Poincar\'e (2009) to appea

The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis

A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia. Furthermore, we demonstrate that decreased expression levels of SDCCAG3 correlate with decreased ciliary length and a reduced percentage of ciliated cells. We show that SDCCAG3 interacts with the intraflagellar transport protein 88 (IFT88), a crucial component of ciliogenesis and intraciliary transport. Mapping experiments revealed that the N-terminus of SDCCAG3 mediates this interaction by binding to a region within IFT88 comprising several tetratricopeptide (TRP) repeats. Finally, we demonstrate that SDCCAG3 is important for ciliary localization of the membrane protein Polycystin-2, a protein playing an important role in the formation of polycystic kidney disease, but not for Rab8 another ciliary protein. Together these data suggest a novel role for SDCCAG3 in ciliogenesis and in localization of cargo to primary cilia

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

Treatment planning for hyperthermia with ultrasound phased arrays.

Hyperthermia cancer therapy applies the cytotoxic effects of heat to tumor cells. All cancer modalities attempt to eliminate malignant cells and minimize normal tissue damage, and for hyperthermia, this involves maximizing therapeutic efficacy and avoiding patient pain. To achieve these goals, a hyperthermia applicator must adapt to individual patients and specific sites, which suggests the application of multiple element arrays. Array systems focus energy within a specified target volume, and, in particular, ultrasound phased arrays allow flexible and precise control of the power deposition. Ultrasound phased arrays provide reasonable values of penetration depth and spot size, crucial parameters for localized hyperthermia in deep tumors. Flexible systems such as ultrasound phased arrays require an optimization procedure prior to each patient treatment. This process, patient treatment planning, consists of thermal, acoustic, and geometric optimization procedures, computations which determine the individual array element amplitudes and phases and which orient the array system relative to the patient. These three routines utilize bioheat transfer, multiple focus synthesis, and ray tracing concepts, respectively. For ultrasound phased arrays, thermal procedures specify an acceptable temperature range both internal and external to the tumor, computing the location and intensity of the necessary focal points, and acoustic methods calculate the element phases and amplitudes corresponding to the requirements of the focal point distribution. In addition, geometric treatment planning maximizes the active aperture and deactivates array elements that irradiate air or bone obstructions. These three steps constitute a framework for hyperthermia treatment planning, where ultrasound phased arrays conform to acoustic windows and deliver preferential heating to a tumor volume. Patient image data for cancer of the prostate, a difficult target situated in the midst of multiple pelvic bone obstructions, illustrates the geometric treatment planning algorithm and other tools for treatment analysis. In addition, the two other procedures demonstrate how ultrasound phased arrays generate acoustic fields which deliver energy to the tumor and distribute power over a wide surface area, reducing undesirable 'hot spots' and surface heating.Ph.D.Electrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104517/1/9527697.pdfDescription of 9527697.pdf : Restricted to UM users only