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Salt Lake City, UT, United States

The University of Utah is a public coeducational space-grant research university in Salt Lake City, Utah, United States. As the state's flagship university, the university offers more than 100 undergraduate majors and more than 92 graduate degree programs. Graduate studies include the S.J. Quinney College of Law and the School of Medicine, Utah's only medical school. As of Autumn 2012, there are 24,840 undergraduate students and 7,548 graduate students, for an enrollment total of 32,388; with 83% coming from Utah and 9% coming from foreign countries. Just over 10% of students live on campus.The university's athletic teams, the Utes, participate in NCAA Division I athletics as a member of the Pacific-12 Conference. Its football team has received national attention in recent years for winning the 2005 Fiesta Bowl and the 2009 Sugar Bowl.The university was established in 1850 as the University of Deseret by the General Assembly of the provisional State of Deseret, making it Utah's oldest institution of higher education. It received its current name in 1892, four years before Utah attained statehood, and moved to its current location in 1900. Wikipedia.


Sensale-Rodriguez B.,University of Utah
Applied Physics Letters | Year: 2013

This work theoretically explores the perspectives of stacked graphene-insulator-graphene layers as active terahertz devices. Out-of-plane resonant tunneling current between the graphene layers is shown to constitute a gain medium for electron-plasma-waves propagating in the plane of the graphene sheets. The interaction between both phenomena can lead to either stable THz amplification (with power gain >7 dB) or very sensitive terahertz detection (with sensitivity >105 V/W) under appropriate device configurations. © 2013 AIP Publishing LLC.


Carbone P.S.,University of Utah
Academic Pediatrics | Year: 2013

Autism spectrum disorders (ASD), once thought rare, are now commonly encountered in clinical practice. Academic pediatricians may be expected to teach medical students and pediatric residents about ASD, but most likely received limited exposure to ASD during their training. In recent years, research that informs the clinical guidance provided to pediatricians regarding surveillance, screening, and ongoing management of children with ASD has accelerated. By 24 months of age, children with ASD exhibit delays across multiple domains of development, yet the diagnosis is frequently made much later. Careful developmental surveillance lowers the age of identification of children with ASD. Several screening tools appropriate for use in primary care settings can aid in early identification. Improved surveillance and screening is of benefit because early intensive behavioral intervention has the potential to improve the developmental trajectory of children with ASD. Providing appropriate medical care for children with ASD improves both child and family outcomes. Recent research regarding sleep disturbances, gastrointestinal problems, and epilepsy in children with ASD has led to clinical pathways to evaluate and address these issues within the context of primary care. By being aware of and disseminating these research findings, academic pediatricians can help future and current clinicians improve the care of children with ASD. Copyright © 2013 by Academic Pediatric Association.


Bromley B.C.,University of Utah
Astrophysical Journal, Supplement Series | Year: 2011

If dark matter self-annihilates then it may produce an observable signal when its density is high. The details depend on the intrinsic properties of dark matter and how it clusters in space. For example, the density profile of some dark matter candidates may rise steeply enough toward the Galactic Center that self-annihilation may produce detectable γ-ray emission. Here, we discuss the possibility that an annihilation signal arises near a compact object (e.g., neutron star or black hole) even when the density of dark matter in the neighborhood of the object is uniform. Gravitational focusing produces a local enhancement of density with a profile that falls off approximately as the inverse square-root of distance from the compact star. While geometric dilution may overwhelm the annihilation signal from this local enhancement, magnetic fields tied to the compact object can increase the signal's contrast relative to the background. © 2011. The American Astronomical Society. All rights reserved.


Morse J.M.,University of Utah
Qualitative Health Research | Year: 2010

Here, I compare the content, characteristics of participants, and the methods used in qualitative health research with qualitative inquiry in general. Special problems that occur when conducting research in an institution, with the emotional content when participants are ill, in pain, or dying, will be discussed. What concerns for the investigator, for the researcher as a person, and methodological quandaries occur? The bottom line is: Do we have a subdiscipline? Is there a need for a special forum for those practicing qualitative health/illness research. © The Author(s) 2010.


Efros A.L.,University of Utah
Physical Review Letters | Year: 2010

The regular Einstein relation, connecting the coefficient of ambipolar diffusion and the Dember field with mobilities, is generalized for the case of an interacting electron-hole plasma. The calculations are presented for a nondegenerate plasma injected by light into semiconductors of silicon and germanium type. The Debye-Huckel correlation and the Wigner-Seitz exchange terms are considered. Corrections to the mobilities of carriers due to the difference between average and acting electric fields within the electron-hole plasma are taken into account. The deviation of the generalized relation from the regular Einstein relation is pronounced at low temperatures and can explain the anomaly of the coefficient of ambipolar diffusion, recently discovered experimentally. © 2010 The American Physical Society.


Brignole M.,Arrhythmologic Center and Syncope Unit | Hamdan M.H.,University of Utah
Journal of the American College of Cardiology | Year: 2012

Significant progress has been made in the past 3 decades in our understanding of the various causes of loss of consciousness thanks to the publication of several important studies and guidelines. In particular, the recent European Society of Cardiology guidelines provide a reference standard for optimal quality service delivery. This paper gives the reader brief guidance on how to manage a patient with syncope, with reference to the above guidelines. Despite the progress made, the management of patients with syncope remains largely unsatisfactory because of the presence of a significant gap between knowledge and its application. Two new concepts aimed at filling that gap are currently under evaluation: syncope facilities with specialist backup and interactive decision-making software. Preliminary data have shown that a standardized syncope assessment, especially when coupled with interactive decision-making software, decreases admission rate and unnecessary testing and improves diagnostic yield, thus reducing cost per diagnosis. The long-term effects of such a new health care model on the rate of diagnosis and survival await future studies. © 2012 American College of Cardiology Foundation.


Wu Y.P.,University of Utah | Pai A.L.H.,Center for Adherence and Self Management
Pediatrics | Year: 2014

BACKGROUND AND OBJECTIVE: Improving medical regimen adherence is essential for maximizing the therapeutic potential of treatments for pediatric chronic illness. Health care providers are uniquely positioned to deliver adherence promotion interventions. However, no studies have summarized the effectiveness of health care provider-delivered adherence interventions. The objective of this study was to describe the effectiveness of health care provider-delivered adherence promotion interventions in improving adherence among children who have chronic illness. Data sources include PubMed, PsycINFO, CINAHL, and Scopus. Studies were included if they were randomized-controlled trials of pediatric interventions aiming to increase adherence to the primary regimen for a chronic illness and at least 1 health care provider delivered the intervention. RESULTS: A total of 35 randomized-controlled studies including 4616 children were included. Greater improvements in adherence were observed immediately after health care provider-delivered interventions (d = 0.49; 95% confidence interval, 0.32 to 0.66) than at longer-term follow-up (d = 0.32; 95% confidence interval, 0.10 to 0.54). Treatment effect sizes differed across the adherence behaviors measured. There was significant heterogeneity in treatment effects; however, no moderators of treatment effectiveness were identified. This meta-analysis focused on the published literature. In addition, the majority of studies involved children who had asthma and younger children. CONCLUSIONS: Health care provider-delivered interventions for children who have chronic illness can be effective in improving adherence. Gains in adherence are highest immediately after intervention. Future interventions and studies should include multiple methods of assessing adherence, include active comparators, and address long-term maintenance of adherence gains. Copyright © 2014 by the American Academy of Pediatrics.


Codding B.F.,University of Utah | Jones T.L.,California Polytechnic State University, San Luis Obispo
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

Global patterns of ethnolinguistic diversity vary tremendously. Some regions show very little variation even across vast expanses, whereas others exhibit dense mosaics of different languages spoken alongside one another. Compared with the rest of Native North America, prehistoric California exemplified the latter. Decades of linguistic, genetic, and archaeological research have produced detailed accounts of the migrations that aggregated to build California's diverse ethnolinguistic mosaic, but there have been few have attempts to explain the process underpinning these migrations and why such a mosaic did not develop elsewhere. Here we show that environmental productivity predicts both the order of migration events and the population density recorded at contact. The earliest colonizers occupied the most suitable habitats along the coast, whereas subsequent Mid-Late Holocene migrants settled in more marginal habitats. Other Late Holocene patterns diverge from this trend, reflecting altered dynamics linked to food storage and increased sedentism. Through repeated migration events, incoming populations replaced resident populations occurring at lower densities in lower-productivity habitats, thereby resulting in the fragmentation of earlier groups and the development of one of the most diverse ethnolinguistic patterns in the Americas. Such a process may account for the distribution of ethnolinguistic diversity worldwide.


Stanley T.H.,University of Utah
Journal of Pain | Year: 2014

Fentanyl, introduced more than 50 years ago, has become the most often used opioid for intraoperative analgesia. Since the early 1990s the fentanyl patch has been available for management of chronic pain of all forms of cancer as well as the persistent, intense pain from many noncancerous maladies. More than a half dozen rapid-onset transmucosal fentanyl preparations have been developed, approved, launched, and popularized for "breakthrough" pain syndromes in the past 20 years. The purpose of this article is to describe why this opioid has become so important in the treatment of pain in modern clinical practice. The data indicate that fentanyl's popularity has occurred because it has minimal cardiovascular effects, does not result in increases in plasma histamine, is relatively short in onset of action and duration of effect, is easy and inexpensive to synthesize and prepare for the marketplace, and is now familiar to clinicians working in pain and perioperative medicine throughout the world.Perspective Fentanyl has become one of the most important opioids in the management of pain because it is available for administration intravenously, transdermally, and transmucosally. Its flexibility, potency, familiarity, and physical characteristics explain why it has become so valuable to clinicians managing pain throughout the world. © 2014 American Pain Society.


Milton G.W.,University of Utah
New Journal of Physics | Year: 2010

We show that any pair of real symmetric tensors ε and μ can be realized as the effective electric permittivity and effective magnetic permeability of a metamaterial at a given fixed frequency. The construction starts with two extremely low-loss metamaterials, with arbitrarily small microstructure, whose existence is ensured by the work of Bouchitté and Bourel and Bouchitté and Schweizer: one having, at the given frequency, a permittivity tensor with exactly one negative eigenvalue, and a positive permeability tensor; and the other having a positive permittivity tensor, and a permeability tensor having exactly one negative eigenvalue. To achieve the desired effective properties, these materials are laminated together in a hierarchical multiple rank laminate structure, with widely separated length scales, and varying directions of lamination, but with the largest length scale still much shorter than the wavelengths and attenuation lengths in the macroscopic effective medium. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


An eigenfunction expansion technique, based in part on separation of the thickness-variable and partly on the Eshelby-Stroh type affine transformation, is employed to derive hitherto unavailable three-dimensional asymptotic stress field in the vicinity of the front of a semi-infinite through-thickness crack weakening an infinite transversely isotropic unidirectional fiber reinforced composite plate, of finite thickness and subjected to far-field mode I/II loadings. Crack-face boundary conditions and those that are prescribed on the top and bottom (free, fixed or lubricated) surfaces of the lamina are exactly satisfied. The present investigation considers mainly two through-crack systems - (i) (0. 1. 0)[0. 0. 1] with the [1. 0. 0] propagation direction, and (ii) (1̄00)[001] with the [0. 1. 0] propagation direction. Explicit expressions for the singular stresses in the vicinity of the front of a through-thickness crack weakening a transversely isotropic unidirectional fiber reinforced composite plate, subjected to far-field mode I/II loadings, are presented. Hitherto unavailable numerical results, pertaining to the through-thickness variations of stress intensity factors for saw-tooth load and its skew-symmetric counterpart that also satisfy the boundary conditions on the top and bottom surfaces of the cracked unidirectional fiber reinforced composite (transversely isotropic) plates under investigation, bridge a longstanding gap in the fracture mechanics literature. © 2010 Elsevier Ltd.


Riede T.,University of Utah
Journal of Experimental Biology | Year: 2010

Fundamental frequency is an important perceptual parameter for acoustic communication in mammals. It is determined by vocal fold oscillation, which depends on the morphology and viscoelastic properties of the oscillating tissue. In this study, I tested if stress-strain and stress-relaxation behavior of rhesus monkey (Macaca tnulatta) vocal folds allows the prediction of a species' natural fundamental frequency range across its entire vocal repertoire as well as of frequency contours within a single call type. In tensile tests, the load-strain and stress-relaxation behavior of rhesus monkey vocal folds and ventricular folds has been examined. Using the string model, predictions about the species' fundamental frequency range, individual variability, as well as the frequency contour of 'coo' calls were made. The low- and mid-frequency range (up to 2 kHz) of rhesus monkeys can be predicted relatively well with the string model. The discrepancy between predicted maximum fundamental frequency and what has been recorded in rhesus monkeys is currently ascribed to the difficulty in predicting the behavior of the lamina propria at very high strain. Histological sections of the vocal fold and different staining techniques identified collagen, elastin, hyaluronan and, surprisingly, fat cells as components of the lamina propria. The distribution of all four components is not uniform, suggesting that different aspects of the lamina propria are drawn into oscillation depending on vocal fold tension. A differentiated recruitment of tissue into oscillation could extend the frequency range specifically at the upper end of the frequency scale. © 2010. Published by The Company of Biologists Ltd.


Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the elderly. An estimated 5.4 million people in the United States have AD, and its prevalence is expected to increase rapidly in the coming years. Few US Food and Drug Administration (FDA)-approved treatment options for AD are currently available. Donepezil is 1 of only 2 therapies approved in the United States for the treatment of moderate-to-severe AD. In 2010, the FDA approved a higher daily dose of donepezil (23 mg/day) for the treatment of AD in the moderate-to-severe stages based on positive results from a large, global, phase 3 clinical trial that compared switching to donepezil 23 mg/day with continuing treatment with donepezil 10 mg/day. In that trial, no benefit was seen in the co-primary endpoint of global functioning; however, donepezil 23 mg/day provided a small but significant improvement in the cognitive endpoint compared with donepezil 10 mg/day. A subgroup analysis subsequently showed that the cognitive benefits were significant irrespective of concomitant memantine use. Adverse events were mainly gastrointestinal related and were more prevalent in patients receiving the donepezil 23-mg/day dose during the first month of therapy, but were relatively infrequent thereafter. These data indicate that once-daily donepezil 23 mg may be an effective treatment option for patients with moderate-to-severe AD with or without concomitant memantine. This article reviews the rationale for using higher-dose donepezil, the clinical data supporting its use, and some of the practical implications that should be considered by practicing physicians when using donepezil 23 mg/day for patients with AD. © Postgraduate Medicine.


Zanno L.E.,University of Utah
Zoological Journal of the Linnean Society | Year: 2010

Falcarius utahensis, from the lower Yellow Cat Member of the Cedar Mountain Formation, represents the most complete and morphologically primitive therizinosaur yet discovered. Since initial publication, only the braincase, pectoral girdle, and forelimb of this phylogenetically important taxon have been subject to detailed investigation. This work completes the description of skeletal material prepared from the Crystal Geyser Quarry subsequent to the first five years of excavation - including elements of the skull, axial column, pelvis, and hind limb of this phylogenetically critical theropod - and presents an emended and significantly expanded diagnosis. Results of this study reveal a significant degree of morphological disparity between Falcarius utahensis and the evidently coeval primitive therizinosaur Beipiaosaurus inexpectus from the Yixian Formation, People's Republic of China and help characterize morphological transformations occurring in the therizinosaur lineage that are of phylogenetic significance, particularly with regard to the highly derived presacral axial column. Finally, Falcarius documents that marked heterodonty - characterized by elongate, incisiform rostral teeth - is present in basal therizinosaurs and oviraptorosaurs (i.e. Incisivosaurus gauthieri, Protarchaeopteryx robusta), and either represents a synapomorphy or symplesiomorphy for these groups or an early phase in the convergent progression toward rostral endentulism. Nonetheless, heterodonty suggests that diet was a primary factor in the early evolution of both clades. © 2010 The Linnean Society of London.


This article comments on: Cutting xylem under tension or supersaturated with gas can generate PLC and the appearance of rapid recovery from embolism © 2013 John Wiley & Sons Ltd.


Shugart H.A.,University of Utah
Obesity Reviews | Year: 2013

In studies of mediated representations of obesity to date, the overwhelming majority have found predominant a personal responsibility frame, specifically as drawn against environmental frames, which are nonetheless gaining ground in recent years. In this essay, I review that extant literature and seek to trouble the binary by isolating national news coverage of obesity in two historically and culturally specific regions of the United States that are regularly referenced in relation to the issue: the South and the Midwest. I evaluate the key characterizations of obesity and obese individuals in these regions in mainstream national news coverage between January 2009 and December 2012 in order to assess whether, how, and to what extent personal responsibility or environmental frames are invoked in this coverage. I argue that 'culture' appears to be gaining traction as an emergent discourse for obesity, which may appear to offer a more complex or nuanced explanation of the issue; however, this analysis suggests that it can be taken up in ways that feature troubling implications and consequences. © 2013 International Association for the Study of Obesity.


Fine P.G.,University of Utah
Pain Medicine | Year: 2012

Background. Chronic or persistent pain is a common problem in older adults and is often associated with significant physical disability and psychosocial problems. The potential benefits, risks, and costs of pharmacotherapy as a mainstay in the treatment of moderate to severe pain in this population must be well-understood and weighed accordingly. Recent treatment guidelines have been introduced that can guide decision making to optimize pain-related treatment outcomes in older individuals Objectives and Results. This review article describes and summarizes key evidence-based recommendations that were derived by a committee convened by the American Geriatrics Society in order to provide guidance to optimize pharmacotherapy in the management of persistent pain in older individuals. Conclusions. It is postulated that ongoing education of clinicians who treat older patients with persistent moderate to severe pain will lead to improved outcomes in this vulnerable population. © 2012.


Pace N.L.,University of Utah
Best Practice and Research: Clinical Anaesthesiology | Year: 2011

Meta-analysis uses numerical tools to pool data and to estimate a summary effect size for the comparison of two interventions from a set of randomised controlled trials identified in a systematic review. An effect size is a single number that expresses the difference in outcome from the interventions. The most commonly used effect sizes for dichotomous outcomes, for example, mortality, are the odds ratio and the relative risk. The results of a meta-analysis are usually presented in a complex figure, known as a forest plot, which shows both the individual studies and the summary statistics. Sensitivity analyses are performed to clarify the effect of the experimental design bias on the effect size. Clinical and statistical heterogeneity of the included studies are explored by the additional tools of fixed effect versus random effects models and subgroup analyses. © 2011 Elsevier Ltd. All rights reserved.


Tashjian R.Z.,University of Utah
Clinics in Sports Medicine | Year: 2012

Rotator cuff disease is the most common shoulder disorder treated by orthopedic surgeons. Little information exits regarding its prevalence and natural history. The prevalence of rotator cuff tearing increases with age as well as several other factors including smoking and family history. Knowledge regarding the natural history of nonoperatively treated tears as well as the healing potential after repair can be used to aid in refining surgical and nonsurgical indications for the treatment rotator cuff tears. An algorithmic approach to the treatment of rotator cuff tears is reviewed. © 2012.


Chrastil J.,University of Utah | Patel A.A.,Loyola University Chicago
Journal of the American Academy of Orthopaedic Surgeons | Year: 2012

Posterior lumbar interbody fusion and transforaminal lumbar interbody fusion are commonly performed to obtain a 360° arthrodesis through a posterior-only approach. These techniques are currently used in the management of spondylolisthesis, degenerative scoliosis, pseudarthrosis, recurrent disk herniation, and chronic low back pain with associated degenerative disk disease. Several adverse events have been described, including intraoperative neurologic injury, implant migration or subsidence, dural tears, infection, heterotopic ossification, BMP-related radiculitis, and osteolysis. Although the use of newer materials (eg, bone morphogenetic proteins) and procedures (eg, minimally invasive surgery) is on the rise, they are associated with unique concerns. Understanding the potential adverse events and steps that can be taken to prevent, detect, and manage complications is critical in patient counseling and perioperative decision making.


Corneli H.M.,University of Utah
Pediatric Emergency Care | Year: 2012

Accidental hypothermia has produced many cases of intact survival even after prolonged cardiac arrest, but it is also often fatal. In recent years, alterations in resuscitation care that sometimes confused or discouraged resuscitation teams have largely been supplanted by an emphasis on safe, rapid, effective rewarming. Rewarming decisions and even the simple recognition of hypothermia remain challenging. This review seeks to update and demystify some of these challenges. Copyright © 2012 by Lippincott Williams & Wilkins.


Ekstrand J.J.,University of Utah
Seminars in Pediatric Neurology | Year: 2012

Neurologic complications associated with influenza infection represent rare, but often underappreciated, manifestations of both seasonal and global pandemic influenza. Seizures are the most common neurologic complication, occurring as febrile seizures, as exacerbations in patients with epilepsy, or as symptoms of other influenza-induced neurologic disorders. Encephalopathy is the second most common neurologic complication associated with influenza. A wide spectrum of conditions ranging from coma with severe long-term morbidity or mortality and more mild altered mental states that resolve with minimal-to-no sequelae have been reported. Other less common neurologic complications that have been described include stroke, focal neurologic deficits, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and transverse myelitis. © 2012 Elsevier Inc.


Mindfulness has been described as a practice of learning to focus attention on moment-bymoment experience with an attitude of curiosity, openness, and acceptance. Mindfulness practices have become increasingly popular as complementary therapeutic strategies for a variety of medical and psychiatric conditions. This paper provides an overview of three mindfulness interventions that have demonstrated effectiveness for psychiatric symptoms and/or pain. The goal of this review is to provide a synopsis that practicing clinicians can use as a clinical reference concerning Zen meditation, mindfulness-based stress reduction (MBSR), and mindfulness-based cognitive therapy (MBCT). All three approaches originated from Buddhist spiritual practices, but only Zen is an actual Buddhist tradition. MBSR and MBCT are secular, clinically based methods that employ manuals and standardized techniques. Studies indicate that MBSR and MBCT have broad-spectrum antidepressant and antianxiety effects and decrease general psychological distress. MBCT is strongly recommended as an adjunctive treatment for unipolar depression. The evidence suggests that both MBSR and MBCT have efficacy as adjunctive interventions for anxiety symptoms. MBSR is beneficial for general psychological health and stress management in those with medical and psychiatric illness as well as in healthy individuals. Finally, MBSR and Zen meditation have a role in pain management. (Journal of Psychiatric Practice 2012;18:233-252) Copyright © 2012 Lippincott Williams & Wilkins Inc.


Carroll D.,University of Utah | Charo R.A.,University of Wisconsin - Madison
Genome Biology | Year: 2015

The genome editing platforms currently in use have revolutionized the field of genetics. At an accelerating rate, these tools are entering areas with direct impact on human well being. Here, we discuss applications in agriculture and in medicine, and examine some associated societal issues. © 2015 Carroll and Charo.


Burbidge S.K.,University of Utah
Preventive Medicine | Year: 2010

Objective: US transportation systems have been identified as a problem for public health, as they often encourage automobile transportation and discourage physical activity. This paper provides a case study examination of the Public Health Component of the Wasatch Front Regional Council's Regional Transportation Plan. This plan provides an example of what transportation planners at Utah's largest metropolitan planning organization (MPO) are doing to encourage physical activity through transportation. Methods: Existing active living research was used to guide recommendations using a process that included a comprehensive literature review and a review of existing state programs, advisory group and stakeholder meetings, and policy recommendations based on existing local conditions. Results: Stakeholders from a diversity of background and interests came together with one common goal: to improve public health. Based on this collaborative process, nine policy approaches were specifically recommended for approval and integration in the Wasatch Front Regional Transportation Plan. Conclusion: By using current research as a guide and integrating a variety of interests, the Wasatch Front Regional Council is setting a new standard for a collaborative multi-modal focus in transportation planning, which can be replicated nationwide. © 2009 Elsevier Inc. All rights reserved.


Painter P.,University of Utah | Roshanravan B.,University of Washington
Current Opinion in Nephrology and Hypertension | Year: 2013

Purpose of Review: Despite guidelines supporting the regular assessment of physical functioning and encouragement of physical activity in management of the patient with chronic kidney disease (CKD), implementation has been undermined by a lack of understanding of the evidence for this recommendation. The purpose of this review is to present a summary of emerging data from larger epidemiologic cohorts that report associations between low levels of physical functioning and/or low physical activity and clinical outcomes in patients with CKD. Recent Findings: Low levels of physical activity and poor physical functioning are strongly associated with mortality and poor clinical outcomes in adult patients with CKD, regardless of treatment modality. Low physical performance and activity limitations are more prevalent in patients with CKD, regardless of age, compared to older community-dwelling adults. Summary: The strength of the evidence presented should strongly motivate a focus of treatment on assessing and improving physical activity and physical function as part of routine patient-centered management of persons with CKD. Physical activity interventions are warranted because patients with CKD, regardless of age, have a high prevalence of low physical functioning and frailty that is similar to or higher than the general population of elderly adults; physical activity, physical function, and performance are strongly associated with all-cause mortality; and exercise training and exercise counseling have been shown to improve measures of physical functioning. Copyright © 2013 Lippincott Williams & Wilkins.


Wei R.,University of Utah
International Regional Science Review | Year: 2016

Achieving maximal coverage of service facilities has been of great interest to urban and regional planners. Examples include placing cellular towers, siting emergency response stations, and locating weather radars, among others. In some planning contexts, facilities could be sited almost anywhere in a region due to their small geographic footprints and demand is continuously distributed. This location problem has been represented as the continuous space maximal coverage problem (CSMCP). The CSMCP is widely acknowledged to be challenging to solve exactly. A broadly used solution approach for the CSMCP is to transform the problem into discrete maximal coverage models through continuous space discretization. A variety of discrete simplifications of CSMCP have been developed, attempting to address spatial representation issues that arise in the application of discrete models used as a continuous space approximation. However, the performance of applying these discrete coverage models to approximately solving the CSMCP has not been explicitly evaluated. It remains elusive as to which approach provides the best approximation for the CSMCP. This article therefore presents a comparative performance analysis of various discrete approximations for the CSMCP. Empirical results provide insights on how to achieve a balance between model representation detail and reasonable computation. Potential research directions are also suggested. © 2015, © The Author(s) 2015.


Kenyon S.J.,Smithsonian Astrophysical Observatory | Bromley B.C.,University of Utah
Astrophysical Journal, Supplement Series | Year: 2010

We describe comprehensive calculations of the formation of icy planets and debris disks at 30-150 AU around 1-3M · stars. Disks composed of large, strong planetesimals produce more massive planets than disks composed of small, weak planetesimals. The maximum radius of icy planets ranges from ∼ 1500km to 11,500km. The formation rate of 1000km objects - "Plutos" - is a useful proxy for the efficiency of icy planet formation. Plutos form more efficiently in massive disks, in disks with small planetesimals, and in disks with a range of planetesimal sizes. Although Plutos form throughout massive disks, Pluto production is usually concentrated in the inner disk. Despite the large number of Plutos produced in many calculations, icy planet formation is inefficient. At the end of the main sequence lifetime of the central star, Plutos contain less than 10% of the initial mass in solid material. This conclusion is independent of the initial mass in the disk or the properties of the planetesimals. Debris disk formation coincides with the formation of planetary systems containing Plutos. As Plutos form, they stir leftover planetesimals to large velocities. A cascade of collisions then grinds the leftovers to dust, forming an observable debris disk. In disks with small (≲1-10km) planetesimals, collisional cascades produce luminous debris disks with maximum luminosity ∼ 10-2 times the stellar luminosity. Disks with larger planetesimals produce debris disks with maximum luminosity 5 × 10-4 (10km) to ∼ 5 × 10-5 (100km) times the stellar luminosity. Following peak luminosity, the evolution of the debris disk emission is roughly a power law, f α t -n with n ≈ 0.6-0.8. Observations of debris disks around A-type and G-type stars strongly favor models with small planetesimals. In these models, our predictions for the time evolution and detection frequency of debris disks agree with published observations. We suggest several critical observations that can test key features of our calculations. © 2010. The American Astronomical Society. All rights reserved.


Brooks B.D.,Wasatch Microfluidics | Brooks A.E.,University of Utah | Brooks A.E.,North Dakota State University
Advanced Drug Delivery Reviews | Year: 2014

With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance. © 2014 Elsevier B.V.


Virkar A.V.,University of Utah
International Journal of Hydrogen Energy | Year: 2010

An electrochemical model for degradation of solid oxide electrolyzer cells is presented. The model is based on concepts in local thermodynamic equilibrium in systems otherwise in global thermodynamic non-equilibrium. It is shown that electronic conduction through the electrolyte, however small, must be taken into account for determining local oxygen chemical potential, μO2, within the electrolyte. The μO2 within the electrolyte may lie out of bounds in relation to values at the electrodes in the electrolyzer mode. Under certain conditions, high pressures can develop in the electrolyte just near the oxygen electrode/electrolyte interface, leading to oxygen electrode delamination. These predictions are in accord with the reported literature on the subject. Development of high pressures may be avoided by introducing some electronic conduction in the electrolyte. © 2010 Published by Elsevier Ltd on behalf of Professor T. Nejat Veziroglu.


Mione M.C.,FIRC Institute of Molecular Oncology Foundation | Trede N.S.,University of Utah
DMM Disease Models and Mechanisms | Year: 2010

For the last three decades significant parts of national science budgets, and international and private funding worldwide, have been dedicated to cancer research. This has resulted in a number of important scientific findings. Studies in tissue culture have multiplied our knowledge of cancer cell pathophysiology, mechanisms of transformation and strategies of survival of cancer cells, revealing therapeutically exploitable differences to normal cells. Rodent animal models have provided important insights on the developmental biology of cancer cells and on host responses to the transformed cells. However, the rate of death from some malignancies is still high, and the incidence of cancer is increasing in the western hemisphere. Alternative animal models are needed, where cancer cell biology, developmental biology and treatment can be studied in an integrated way. The zebrafish offers a number of features, such as its rapid development, tractable genetics, suitability for in vivo imaging and chemical screening, that make it an attractive model to cancer researchers. This Primer will provide a synopsis of the different cancer models generated by the zebrafish community to date. It will discuss the use of these models to further our understanding of the mechanisms of cancer development, and to promote drug discovery. The article was inspired by a workshop on the topic held in July 2009 in Spoleto, Italy, where a number of new zebrafish cancer models were presented. The overarching goal of the article is aimed at raising the awareness of basic researchers, as well as clinicians, to the versatility of this emerging alternative animal model of cancer. © 2010. Published by The Company of Biologists Ltd.


Stewart R.J.,University of Utah
Applied Microbiology and Biotechnology | Year: 2011

Biotechnological approaches to practical production of biological protein-based adhesives have had limited success over the last several decades. Broader efforts to produce recombinant adhesive proteins may have been limited by early disappointments. More recent synthetic polymer approaches have successfully replicated some aspects of natural underwater adhesives. For example, synthetic polymers, inspired by mussels, containing the catecholic functional group of 3,4-L-dihydroxyphenylalanine adhere strongly to wet metal oxide surfaces. Synthetic complex coacervates inspired by the Sandcastle worm are water-borne adhesives that can be delivered underwater without dispersing. Synthetic approaches offer several advantages, including versatile chemistries and scalable production. In the future, more sophisticated mimetic adhesives may combine synthetic copolymers with recombinant or agriculture-derived proteins to better replicate the structural and functional organization of natural adhesives. © 2010 Springer-Verlag.


Garrett T.J.,University of Utah
Climatic Change | Year: 2011

Global Circulation Models (GCMs) provide projections for future climate warming using a wide variety of highly sophisticated anthropogenic CO2 emissions scenarios as input, each based on the evolution of four emissions "drivers": population p, standard of living g, energy productivity (or efficiency) f and energy carbonization c (IPCC WG III 2007). The range of scenarios considered is extremely broad, however, and this is a primary source of forecast uncertainty (Stott and Kettleborough, Nature 416:723-725, 2002). Here, it is shown both theoretically and observationally how the evolution of the human system can be considered from a surprisingly simple thermodynamic perspective in which it is unnecessary to explicitly model two of the emissions drivers: population and standard of living. Specifically, the human system grows through a self-perpetuating feedback loop in which the consumption rate of primary energy resources stays tied to the historical accumulation of global economic production-or p×g-through a time-independent factor of 9.7±0.3 mW per inflation-adjusted 1990 US dollar. This important constraint, and the fact that f and c have historically varied rather slowly, points towards substantially narrowed visions of future emissions scenarios for implementation in GCMs. © 2009 The Author(s).


Garland E.L.,University of Utah | Howard M.O.,University of North Carolina at Chapel Hill
Psychotherapy and Psychosomatics | Year: 2013

Background: Chronic pain involves hypervigilance for pain-related stimuli. Selective attention to pain-related stimuli, known as pain attentional bias (AB), can exacerbate chronic pain, prolong suffering, and undermine quality of life. The aim of this study was to determine if a multimodal mindfulness-oriented intervention could significantly reduce pain AB among chronic pain patients receiving opioid analgesics. Methods: A total of 67 chronic pain patients were randomized to an 8-week Mindfulness-Oriented Recovery Enhancement (MORE) intervention or a social support group intervention and began treatment. A dot probe task was used to measure pain AB. Primary outcomes were pain AB scores for cues presented for 2,000 and 200 ms. Results: Prior to intervention, participants exhibited a significant bias towards pain-related cues presented for 2,000 ms, but no bias for cues presented for 200 ms. A statistically significant time × intervention condition interaction was observed for 2,000 ms pain AB, such that participants in MORE evidenced significantly reduced posttreatment pain AB relative to pretreatment levels, whereas no significant pre-post treatment changes in pain AB were observed for support group participants. Decreases in pain AB were associated with increased perceived control over pain and attenuated reactivity to distressing thoughts and emotions. Conclusion: Study findings provide the first indication that a mindfulness-oriented intervention may reduce pain AB among adults suffering from chronic pain. Given the magnitude of chronic pain in postindustrial societies, coupled with the dramatic escalation in prescription opioid misuse, future studies should evaluate MORE as a nonpharmacological means of addressing factors linked with chronic pain. © 2013 S. Karger AG, Basel.


A modified form of the Townsend equations for the fluctuating velocity wave vectors is applied to a laminar three-dimensional boundary-layer flow. These equations are cast into a Lorenz-type system of equations. The initial system of Lorenz equations yields the generation of masked output signals containing internal ordered regions. The selfsynchronizing property of the Lorenz system of equations is then exploited by considering the initial Lorenz system as a transmitter system providing chaotic masked information signals to a series of identical Lorenz receiver systems. The output signal from each successive receiver system indicates the growing recovery of ordered regions in the chaotic output signal. Finally, the three-dimensional graph of the output velocity wave vector signal from the fourth receiver system and the spectral entropy rates for the output axial velocity wave vector indicate the presence of ordered regions which are characterized as axially-directed spiral vortices. © 2013 by the authors.


Planelles V.,University of Utah
Viruses | Year: 2011

The lentiviral accessory protein, Vpx, is known to counteract a restriction factor that is specific to myeloid cells, such as macrophages and dendritic cells. This review summarizes the findings in two seminal studies that identify SAMHD1 as the cellular protein that is responsible for myeloid cell restriction, and establish the existence of other types of restriction in these cells. © 2011 by the authors; licensee MDPI, Basel, Switzerland.


Craig R.K.,University of Utah
Harvard Environmental Law Review | Year: 2012

The variety of anthropogenic stressors to the marine environment-including, increasingly, climate change and their complex and synergistic impacts on ocean ecosystems testifies to the failure of existing governance regimes to protect these ecosystems and the services that they provide. Marine spatial planning has been widely hailed as a means of improving ocean governance through holistic ecosystem-based planning. However, that concept arose without reference to climate change, and hence it does not automatically account for the dynamic alterations in marine ecosystems that climate change is bringing. This Article attempts to adapt marine spatial planning to climate change adaptation. In so doing, it explores three main topics. First, it examines how established marine protected areas can aid climate change adaptation. Second, it looks at how nations have incorporated climate change considerations into marine spatial planning to increase marine ecosystem resilience, focusing on the international leader in marine spatial planning: Australia. Finally, the Article explores how marine spatial planning could become flexible enough to adapt to the changes that climate change will bring to the world's oceans, focusing on anticipatory zoning. Governments, of course, can establish marine zoning governance regimes in anticipation of climate change impacts, as has already occurred in the Arctic. However, drawing on work by Josh Eagle, Barton H. Thompson, and James Sanchirico, this Article argues that governments could also combine anticipatory zoning and comprehensively regulated marine use rights bidding regimes to encourage potential future private users to make informed bets about the future productivity value of different parts of the ocean, potentially improving both our ability to anticipate climate change impacts on particular marine environments and the ocean governance regimes for climatesensitive areas.


Zhdanov M.S.,University of Utah
Geophysics | Year: 2010

During the last century, electrical geophysics has been transformed from a simple resistivity method to a modern technology that uses complex data-acquisition systems and high-performance computers for enhanced data modeling and interpretation. Not only the methods and equipment have changed but also our ideas about the geoelectrical models used for interpretation have been modified tremendously. This paper describes the evolution of the conceptual and technical foundations of EM methods. It outlines a framework for further development, which should focus on multitransmitter and multireceiver surveys, analogous to seismic data-acquisition systems. Important potential topics of future research efforts are in the areas of multidimensional modeling and inversion, including a new approach to the formulation and understanding of EM fields based on flux and voltage representation, which corresponds well to geophysical experiments involving the measurement of voltage and flux of electric and magnetic fields. © 2010 Society of Exploration Geophysicists.


Vocal production requires complex planning and coordination of respiratory, laryngeal, and vocal tract movements, which are incompletely understood in most mammals. Rats produce a variety of whistles in the ultrasonic range that are of communicative relevance and of importance as a model system, but the sources of acoustic variability were mostly unknown. The goal was to identify sources of fundamental frequency variability. Subglottal pressure, tracheal airflow, and electromyographic (EMG) data from two intrinsic laryngeal muscles were measured during 22-kHz and 50-kHz call production in awake, spontaneously behaving adult male rats. During ultrasound vocalization, subglottal pressure ranged between 0.8 and 1.9 kPa. Pressure differences between call types were not significant. The relation between fundamental frequency and subglottal pressure within call types was inconsistent. Experimental manipulations of subglottal pressure had only small effects on fundamental frequency. Tracheal airflow patterns were also inconsistently associated with frequency. Pressure and flow seem to play a small role in regulation of fundamental frequency. Muscle activity, however, is precisely regulated and very sensitive to alterations, presumably because of effects on resonance properties in the vocal tract. EMG activity of cricothyroid and thyroarytenoid muscle was tonic in calls with slow or no fundamental frequency modulations, like 22-kHz and flat 50-kHz calls. Both muscles showed brief high-amplitude, alternating bursts at rates up to 150 Hz during production of frequencymodulated 50-kHz calls. A differentiated and fine regulation of intrinsic laryngeal muscles is critical for normal ultrasound vocalization. Many features of the laryngeal muscle activation pattern during ultrasound vocalization in rats are shared with other mammals. © 2011 the American Physiological Society.


Bromley B.C.,University of Utah | Kenyon S.J.,Smithsonian Astrophysical Observatory
Astrophysical Journal | Year: 2011

We describe an updated version of our hybrid N-body-coagulation code for planet formation. In addition to the features of our 2006-2008 code, our treatment now includes algorithms for the one-dimensional evolution of the viscous disk, the accretion of small particles in planetary atmospheres, gas accretion onto massive cores, and theresponse of N-bodies to the gravitational potential of the gaseous disk and the swarm of planetesimals. To validate the N-body portion of the algorithm, we use a battery of tests in planetary dynamics. As a first application of the complete code, we consider the evolution of Pluto-mass planetesimals in a swarm of 0.1-1 cm pebbles. In a typical evolution time of 1-3 Myr, our calculations transform 0.01-0.1 M ⊙ disks of gas and dust into planetary systems containing super-Earths, Saturns, and Jupiters. Low-mass planets form more often than massive planets; disks with smaller α form more massive planets than disks with larger α. For Jupiter-mass planets, masses of solid cores are 10-100 M ⊕. © 2011. The American Astronomical Society. All rights reserved.


Basu S.,Arizona State University | Francoeur M.,University of Utah
Optics Letters | Year: 2014

We investigate near-field radiative heat transfer between two thin films made of metamaterials. The impact of film thickness on magnetic and electric surface polaritons (ESPs) is analyzed. It is found that the strength as well as the location of magnetic resonance does not change with film thickness until the film behaves as semi-infinite for the dielectric function chosen in this study. When the film is thinner than vacuum gap, both electric and magnetic polaritons contribute evenly to near-field radiative heat transfer. At larger film thicknesses, ESPs dominate heat transfer due to excitation of a larger number of modes. Results obtained from this study will facilitate applications of metamaterials as thin-film coatings for energy systems. © 2014 Optical Society of America.


Bromley B.C.,University of Utah | Kenyon S.J.,Smithsonian Astrophysical Observatory
Astrophysical Journal | Year: 2011

Planetary migration poses a serious challenge to theories of planet formation. In gaseous and planetesimal disks, migration can remove planets as quickly as they form. To explore migration in a planetesimal disk, we combine analytic and numerical approaches. After deriving general analytic migration rates for isolated planets, we use N-body simulations to confirm these results for fast and slow migration modes. Migration rates scale as m -1 (for massive planets) and (1 + (e H/3)3)-1, where m is the mass of a planet and e H is the eccentricity of the background planetesimals in Hill units. When multiple planets stir the disk, our simulations yield the new result that large-scale migration ceases. Thus, growing planets do not migrate through planetesimal disks. To extend these results to migration in gaseous disks, we compare physical interactions and rates. Although migration through a gaseous disk is an important issue for the formation of gas giants, we conclude that migration has little impact on the formation of terrestrial planets. © 2011. The American Astronomical Society. All rights reserved..


Parker C.J.,University of Utah
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Despite the availability of safe, effective targeted therapy that controls intravascular hemolysis, the management of paroxysmal nocturnal hemoglobinuria (PNH) remains complicated because of disease heterogeneity and close association with BM failure syndromes. The purpose of this review is to provide a framework for individualizing treatment based on disease classification. According to the recommendations of the International PNH Interest Group, patients can be placed into one of the following 3 categories: (1) classic PNH, (2) PNH in the setting of another BM failure syndrome, or (3) subclinical PNH. The PNH clone in patients with subclinical disease is insufficiently large to produce even biochemical evidence of hemolysis, and consequently, patients who fit into this category require no PNH-specific therapy. Patients with PNH in the setting of another BM failure syndrome (usually aplastic anemia or low-risk myelodysplastic syndrome) have at least biochemical evidence of hemolysis, but typically the PNH clone is small (< 10%) so that hemolysis does not contribute significantly to the underlying anemia. In these cases, the focus of treatment is on the BM failure component of the disease. Intravascular hemolysis is the dominant feature of classic PNH, and this process is blocked by the complement inhibitor eculizumab. The thrombophilia of PNH also appears to be ameliorated by eculizumab, but the drug has no effect on the BM failure component of the disease. Low-grade extravascular hemolysis due to complement C3 opsonization develops in most patients treated with eculizumab, and in some cases is a cause for suboptimal response to treatment. Allogeneic BM transplantation can cure classic PNH, but treatment-related toxicity suggests caution for this approach to management.


Nygaard I.,University of Utah
New England Journal of Medicine | Year: 2010

At least weekly, a 62-year-old kindergarten teacher has a strong sense of urgency to urinate that is followed by urinary leakage while she rushes to the bathroom during her lunch break. She also infrequently leaks drops of urine while exercising. Her medical history is notable for mild hypertension, for which she takes hydrochlorothiazide. On physical examination, she is found to be obese and not to have abdominal masses or clinically significant pelvic-organ prolapse. How should her case be evaluated and treated? Copyright © 2010 Massachusetts Medical Society.


Amann M.,University of Utah
Experimental Physiology | Year: 2012

Accumulating evidence over the past 25 years depicts the healthy pulmonary system as a limiting factor of whole-body endurance exercise performance. This brief overview emphasizes three respiratory system-related mechanisms which impair O 2 transport to the locomotor musculature [arterial O 2 content × leg blood flow], i.e. the key determinant of an individual's aerobic capacity and ability to resist fatigue. First, the respiratory system often fails to prevent arterial desaturation substantially below resting values and thus compromises. Especially susceptible to this threat to convective O 2 transport are well-trained endurance athletes characterized by high metabolic and ventilatory demands and, probably due to anatomical and morphological gender differences, active women. Second, fatiguing respiratory muscle work (W resp) associated with strenuous exercise elicits sympathetically mediated vasoconstriction in limb-muscle vasculature, which compromises. This impact on limb O 2 transport is independent of fitness level and affects all individuals, but only during sustained, high-intensity endurance exercise performed above ∼85% maximal oxygen uptake. Third, excessive fluctuations in intrathoracic pressures accompanying W resp can limit cardiac output and therefore. Exposure to altitude exacerbates the respiratory system limitations observed at sea level, further reducing and substantially increasing exercise-induced W resp. Taken together, the intact pulmonary system of healthy endurance athletes impairs locomotor muscle O 2 transport during strenuous exercise by failing to ensure optimal arterial oxygenation and compromising. This respiratory system-related impact exacerbates the exercise-induced development of fatigue and compromises endurance performance. © 2012 The Author. Journal compilation © 2012 The Physiological Society.


The right ventricle (RV) is the major determinant of functional state and prognosis in pulmonary arterial hypertension. RV hypertrophy (RVH) triggered by pressure overload is initially compensatory but often leads to RV failure. Despite similar RV afterload and mass some patients develop adaptive RVH (concentric with retained RV function), while others develop maladaptive RVH, characterized by dilatation, fibrosis, and RV failure. The differentiation of adaptive versus maladaptive RVH is imprecise, but adaptive RVH is associated with better functional capacity and survival. At the molecular level, maladaptive RVH displays greater impairment of angiogenesis, adrenergic signaling, and metabolism than adaptive RVH, and these derangements often involve the left ventricle. Clinically, maladaptive RVH is characterized by increased N-terminal pro-brain natriuretic peptide levels, troponin release, elevated catecholamine levels, RV dilatation, and late gadolinium enhancement on MRI, increased fluorodeoxyglucose uptake on positron emission tomography, and QTc prolongation on the ECG. In maladaptive RVH there is reduced inotrope responsiveness because of G-protein receptor kinase-mediated downregulation, desensitization, and uncoupling of β-adrenoreceptors. RV ischemia may result from capillary rarefaction or decreased right coronary artery perfusion pressure. Maladaptive RVH shares metabolic abnormalities with cancer including aerobic glycolysis (resulting from a forkhead box protein O1-mediated transcriptional upregulation of pyruvate dehydrogenase kinase), and glutaminolysis (reflecting ischemia-induced cMyc activation). Augmentation of glucose oxidation is beneficial in experimental RVH and can be achieved by inhibition of pyruvate dehydrogenase kinase, fatty acid oxidation, or glutaminolysis. Therapeutic targets in RV failure include chamber-specific abnormalities of metabolism, angiogenesis, adrenergic signaling, and phosphodiesterase-5 expression. The ability to restore RV function in experimental models challenges the dogma that RV failure is irreversible without regression of pulmonary vascular disease. © 2014 American Heart Association, Inc.


Parry W.T.,University of Utah
Sedimentary Geology | Year: 2011

Iron oxide concretions are formed from post depositional, paleogroundwater chemical interaction with iron minerals in porous sedimentary rocks. The concretions record a history of iron mobilization and precipitation caused by changes in pH, oxidation conditions, and activity of bacteria. Transport limited growth rates may be used to estimate the duration of fluid flow events. The Jurassic Navajo Sandstone, an important hydrocarbon reservoir and aquifer on the Colorado Plateau, USA, is an ideal stratum to study concretions because it is widely distributed, well exposed and is the host for a variety of iron oxide concretions. Many of the concretions are nearly spherical and some consist of a rind of goethite that nearly completely fills the sandstone porosity and surrounds a central sandstone core. The interior and exterior host-rock sandstones are similar in detrital minerals, but kaolinite and interstratified illite-smectite are less abundant in the interior. Lepidocrocite is present as sand-grain rims in the exterior sandstone, but not present in the interior of the concretions. Widespread sandstone bleaching resulted from dissolution of early diagenetic hematite grain coatings by chemically reducing water that gained access to the sandstone through fault conduits. The iron was transported in solution and precipitated as iron oxide concretions by oxidation and increasing pH. Iron diffusion and advection growth time models place limits on minimum duration of the diagenetic, fluid flow events that formed the concretions. Concretion rinds 2. mm thick and 25. mm in radius would take place in 2000. years from transport by diffusion and advection and in 3600. years if transport was by diffusion only. Solid concretions 10. mm in radius would grow in 3800. years by diffusion or 2800. years with diffusion and advection. Goethite (α-FeO (OH)) and lepidocrocite (γ-FeO (OH)) nucleated on K-feldspar grains, on illite coatings on sand grains, and on pore-filling illite, but not on clean quartz grains. Model results show that regions of detrital K-feldspar in the sandstone that consume H+ more rapidly than diffusion to the reaction site determine concretion size, and spacing is related to diffusion and advection rates of supply of reactants Fe2+, O2, and H+. © 2010 Elsevier B.V.


Cho H.,Mississippi State University | Smith A.D.,University of Utah | Mago P.,Mississippi State University
Applied Energy | Year: 2014

This paper presents a review on combined cooling, heating, and power (CCHP) systems. This work summarizes the methods used to perform energetic and exergetic analyses, system optimization, performance improvement studies, and development and analysis of CCHP systems, as reported in existing literature. In addition, this work highlights the most current research and emerging trends in CCHP technologies. It is envisioned that the information collected in this review paper will be a valuable source of information, for researchers, designers, and engineers, and provides direction and guidance for future research in CCHP technology. © 2014 Elsevier Ltd.


Dearing M.D.,University of Utah
Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology | Year: 2013

Diet selection in mammalian herbivores is thought to be primarily governed by intrinsic properties of food, such as nutrient and plant secondary compound (PSC) contents, and less so by environmental factors. However, several independent lines of evidence suggest that the toxicity of PSCs is mediated, in part, by ambient temperature and that the effect of small changes in ambient temperature is on par with several fold changes in PSC concentration. This review describes the disparate lines of evidence for temperature-dependent toxicity and the putative mechanisms causing this phenomenon. A model is described that integrates thermal physiology with temperature-dependent toxicity to predict maximal dietary intake of plant secondary compounds by mammalian herbivores. The role of temperature-dependent toxicity is considered with respect to the observed changes in herbivorous species attributed to climate change. Possible future investigations and the effects of temperature-dependent toxicity on other endotherms are presented. Temperature-dependent toxicity has the potential to apply to all endotherms that consume toxins. The effects of temperature-dependent toxicity will likely be exacerbated with increasing ambient temperatures caused by climate change. © 2012 Springer-Verlag.


Planelles V.,University of Utah
Cell Host and Microbe | Year: 2012

The host restriction factor SAMHD1 hinders lentiviral infection of myeloid cells, a function counteracted by the viral protein Vpx. Two papers in this issue of Cell Host & Microbe document the genetic conflict between SAMHD1 and the Vpr/Vpx proteins, which has subjected SAMHD1 to intense periods of diversifying selection through primate evolution. © 2012 Elsevier Inc.


Knight J.A.,University of Utah
Annals of Clinical and Laboratory Science | Year: 2011

Excess body weight is a very serious problem, especially in North America and Europe. It has been referred to as a " pandemic" since it has progressively increased over the past several decades. Moreover, excess body weight significantly increases the risk of numerous diseases and clinical disorders, including all-cause mortality, coronary and cerebrovascular diseases, various cancers, type 2 diabetes mellitus, hypertension, liver disease and asthma, as well as psychopathology, among others. Unfortunately, overweight and obesity are now common in both young children and adolescents. Although the causes of excess body weight are multi-factorial, the most important factors are excess caloric intake coupled with limited energy expenditure. Therefore, lifestyle modification can significantly reduce the risk of morbidity and mortality and thereby increase longevity and improve the quality of life. © 2011 by the Association of Clinical Scientists, Inc.


Smith A.D.,University of Utah | Mago P.J.,Mississippi State University
Applied Energy | Year: 2014

Combined heat and power (CHP) systems can be operated in partial loading situations when the maximum electrical and thermal output of the prime mover is not constantly required by the facility. Two basic load-following methods following the thermal load (FTL) and following the electric load (FEL), are compared with a hybrid method which either follows the thermal or the electric demand in a given time period, within a specified operating range, in order to minimize the amount of excess electrical or thermal energy produced by the CHP system. These methods are implemented on an hour by hour basis for a large hotel benchmark building which is modeled in 16 cities located in different climate zones using EnergyPlus building simulation software. The hybrid method results in a higher total CHP system efficiency than either the FTL or FEL methods, with CHP system efficiency values from 71% to 87%. The power-to-heat ratio of the building (PHRb), which describes the relationship between electrical and thermal demand for the given facility, is found to predict the maximum possible CHP system efficiency using the hybrid method on an hourly basis. Buildings with lower PHRb values, corresponding to higher relative thermal demands, have the highest possible CHP system efficiency values. The hybrid operational method is also implemented on a monthly basis, where the building's average monthly demands are used to set the operating condition of the prime mover for the entire month. The building is then simulated on an hour by hour basis to determine the system's performance with only monthly changes in the loading conditions. This monthly method produces similar results to the hybrid method when it is implemented on an hourly basis, with CHP system efficiency values from 74% to 86%. © 2013 Elsevier Ltd.


Sohn H.Y.,University of Utah
Metallurgical and Materials Transactions B: Process Metallurgy and Materials Processing Science | Year: 2014

It is argued that the term with the negative sign in the rate expression for an equilibrium-limited gas–solid reaction can be viewed as representing a lowering of the concentration driving force for the forward reaction due to equilibrium limitation. While the gas composition favors the forward reaction, the negative term may represent the local rate of the reverse reaction. When the gas composition changes significantly to the opposite side of equilibrium, however, this term as written for the forward reaction does not represent the rate of the reverse reaction. Even the reaction order with respect to the same gaseous species may become different for the reverse reaction. © 2014, The Minerals, Metals & Materials Society and ASM International.


Hollenhorst P.C.,Indiana University | McIntosh L.P.,University of British Columbia | Graves B.J.,University of Utah | Graves B.J.,Howard Hughes Medical Institute
Annual Review of Biochemistry | Year: 2011

ETS proteins are a group of evolutionarily related, DNA-binding transcriptional factors. These proteins direct gene expression in diverse normal and disease states by binding to specific promoters and enhancers and facilitating assembly of other components of the transcriptional machinery. The highly conserved DNA-binding ETS domain defines the family and is responsible for specific recognition of a common sequence motif, 5′-GGA(A/T)-3′. Attaining specificity for biological regulation in such a family is thus a conundrum. We present the current knowledge of routes to functional diversity and DNA binding specificity, including divergent properties of the conserved ETS and PNT domains, the involvement of flanking structured and unstructured regions appended to these dynamic domains, posttranslational modifications, and protein partnerships with other DNA-binding proteins and coregulators. The review emphasizes recent advances from biochemical and biophysical approaches, as well as insights from genomic studies that detect ETS-factor occupancy in living cells. © 2011 by Annual Reviews. All rights reserved.


Thiese M.S.,University of Utah
Biochemia Medica | Year: 2014

The appropriate choice in study design is essential for the successful execution of biomedical and public health research. There are many study designs to choose from within two broad categories of observational and interventional studies. Each design has its own strengths and weaknesses, and the need to understand these limitations is necessary to arrive at correct study conclusions. Observational study designs, also called epidemiologic study designs, are often retrospective and are used to assess potential causation in exposure- outcome relationships and therefore influence preventive methods. Observational study designs include ecological designs, cross sectional, case-control, case-crossover, retrospective and prospective cohorts. An important subset of observational studies is diagnostic study designs, which evaluate the accuracy of diagnostic procedures and tests as compared to other diagnostic measures. These include diagnostic accuracy designs, diagnostic cohort designs, and diagnostic randomized controlled trials. Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease. Each study design has specific outcome measures that rely on the type and quality of data utilized. Additionally, each study design has potential limitations that are more severe and need to be addressed in the design phase of the study. This manuscript is meant to provide an overview of study design types, strengths and weaknesses of common observational and interventional study designs. © Croatian Society of Medical Biochemistry and Laboratory Medicine.


Zhang Q.,University of Utah
Computer Methods in Applied Mechanics and Engineering | Year: 2013

Lagrangian flux through a fixed curve segment within a time interval (t n, t n + k) can be formulated as an integral at the initial time t n over a compact point set called donating region, in which each particle will pass through the curve during the time interval and contribute to the flux. Based an explicit, constructive, and analytical solution of the donating region, the author proposes algorithms of Lagrangian flux calculation (LFC) as algebraic quadratures over the spline-approximated donating regions. This generic formulation yields high accuracies up to the 8th-order both in time and space. As another benefit, LFC leads to a conservative semi-Lagrangian method whose time step size is free of the Eulerian stability constraint C r ≤ 1. The high accuracy and robustness of the proposed LFC algorithms are demonstrated by various numerical tests with Courant numbers ranging from 1 to 10,000 and with accuracies from the 2nd order to the 8th order. LFC might also be useful in designing hybrid Eulerian methods for complex geometries. © 2013 Elsevier B.V.


Hammond D.C.,University of Utah
Expert Review of Neurotherapeutics | Year: 2010

Self-hypnosis training represents a rapid, cost-effective, nonaddictive and safe alternative to medication for the treatment of anxiety-related conditions. Here we provide a review of the experimental literature on the use of self-hypnosis in the treatment of anxiety and stress-related disorders, including anxiety associated with cancer, surgery, burns and medical/dental procedures. An overview of research is also provided with regard to self-hypnotic treatment of anxiety-related disorders, such as tension headaches, migraines and irritable bowel syndrome. The tremendous volume of research provides compelling evidence that hypnosis is an efficacious treatment for state anxiety (e.g., prior to tests, surgery and medical procedures) and anxiety-related disorders, such as headaches and irritable bowel syndrome. Although six studies demonstrate changes in trait anxiety, this review recommends that further randomized controlled outcome studies are needed on the hypnotic treatment of generalized anxiety disorder and in documenting changes in trait anxiety. Recommendations are made for selecting clinical referral sources. © 2010 Expert Reviews Ltd.


Factorovich M.H.,Argentinean Institute of Chemical Physics for Materials, Environment and Energy | Molinero V.,University of Utah | Scherlis D.A.,Argentinean Institute of Chemical Physics for Materials, Environment and Energy
Journal of the American Chemical Society | Year: 2014

Classical thermodynamics is assumed to be valid up to a certain length-scale, below which the discontinuous nature of matter becomes manifest. In particular, this must be the case for the description of the vapor pressure based on the Kelvin equation. However, the legitimacy of this equation in the nanoscopic regime can not be simply established, because the determination of the vapor pressure of very small droplets poses a challenge both for experiments and simulations. In this article we make use of a grand canonical screening approach recently proposed to compute the vapor pressures of finite systems from molecular dynamics simulations. This scheme is applied to water droplets, to show that the applicability of the Kelvin equation extends to unexpectedly small lengths, of only 1 nm, where the inhomogeneities in the density of matter occur within spatial lengths of the same order of magnitude as the size of the object. While in principle this appears to violate the main assumptions underlying thermodynamics, the density profiles reveal, however, that structures of this size are still homogeneous in the nanosecond time-scale. Only when the inhomogeneity in the density persists through the temporal average, as it is the case for clusters of 40 particles or less, do the macroscopic thermodynamics and the molecular descriptions depart from each other. © 2014 American Chemical Society.


Varner J.,University of Utah
BioScience | Year: 2014

Most scientists agree that interacting with the public is a worthwhile endeavor, but participation in science outreach remains fairly low among biologists. Furthermore, current practices in science outreach remain largely based on ineffective communication models that may undermine public trust and interest. I argue that, in trying to improve both participation rates and the effectiveness of science outreach, we must take a more scientific approach, and we must practice outreach with the same rigor as the science that we share with the public. Here, I describe common misconceptions that can undermine the value of science communication with the public at many scales. I then describe an evidence-based, iterative, evaluative framework for biologists at all career stages to pursue public engagement in the biological sciences. These guidelines can also inform formal outreach training for scientists, specifically in promoting dialogue and engagement. © 2014 The Author(s).


Pohl J.F.,University of Utah
Current Opinion in Pediatrics | Year: 2012

PURPOSE OF REVIEW: Clostridium difficile is an intestinal infection associated with antibiotic use, commonly seen in patients with chronic medical issues. The purpose of this review is to discuss the association of C. difficile-associated diarrhea with use of proton pump inhibitors. RECENT FINDINGS: Multiple medical factors predispose patients to C. difficile-associated diarrhea. Proton pump inhibitors, commonly used for gastric acid suppression, have been shown to have an association with C. difficile-associated diarrhea in both the outpatient and hospital setting. C. difficile-associated diarrhea also has been reported in the pediatric age range linked with proton pump inhibitor use. SUMMARY: An association exists between C. difficile infection and proton pump inhibitor use. Treatment options exist for C. difficile-associated diarrhea, although judicious use of proton pump inhibitors and antibiotics, emphasis on hand washing, and appropriate use of patient isolation should be implemented as well. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Armentrout P.B.,University of Utah
Catalysis Science and Technology | Year: 2014

Studies of small gas-phase transition metal cluster cations (2-18 atoms) are reviewed with an emphasis on the thermodynamic information acquired. For the metal-metal bond energies, the cluster results deviate from the bulk-phase enthalpy of vaporization in a manner than can be quantitatively described by the spherical drop model that accounts for the surface free energy using bulk-phase parameters (within 10-20%). Binding energies of atomic H and O adsorbates to such clusters are found to vary extensively for the smallest clusters and to reach values lying close to bulk-phase adsorbate energies for all five metal systems that have been investigated (V, Cr, Fe, Co, and Ni). For molecular fragments (C, CH, CH2, NH, and NH2), binding energies to clusters are also found to plateau for larger clusters (greater than about 10 atoms). These asymptotic values may be useful in estimating such quantities on surfaces. In the case of atomic N adsorbates, variations in the adsorbate energies with cluster size remain appreciable through the size range studied, which appears to be a consequence of activating the very strong N2 bond. © the Partner Organisations 2014.


Brinton E.A.,University of Utah
Current Opinion in Lipidology | Year: 2010

PURPOSE OF REVIEW: This article reviews published studies regarding effects of ethanol intake on lipoprotein levels and function as they relate to atherosclerosis, with special emphasis on recent publications in the past 2 years. RECENT FINDINGS: Some recent studies have explored novel mechanisms of ethanol on atherogenesis via effects on HDL composition and function. Other studies have focused on changes in levels of LDL cholesterol (LDL-C), triglyceride, and other factors such as inflammatory markers C-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (LpPLA2). Other areas of emphasis have been the effects within specific populations and between genders, as well as contributions of genetic polymorphisms in prediction of response to ethanol. Surprisingly, results of recent studies are often at odds with prior, seemingly well established findings. SUMMARY: The association between moderate ethanol consumption and favorable changes in lipoproteins and lipoprotein-related factors in atherosclerosis continues to become better established with the publication of new studies in this field. Continued progress is being achieved in understanding the well established link between moderate intake and reduced risk of cardiovascular disease (CVD). Nevertheless, it remains difficult to implement these findings in clinical practice due to the ongoing lack of randomized, blinded clinical trial data, and the well known hazards of excess ethanol consumption. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Blais R.K.,University of Utah | Renshaw K.D.,George Mason University
Journal of Traumatic Stress | Year: 2013

Many U.S. Iraq/Afghanistan-era veterans return from deployment with posttraumatic stress (PTS) symptoms, but few veterans seek psychological help. Research on barriers to care is growing, but the link between stigma and help-seeking is understudied. The present study examined anticipated enacted stigma from military and nonmilitary sources, self-stigma, PTS, perceived likelihood of deploying again, marital status, and history of mental health care engagement as correlates of help-seeking intentions from a mental health professional or medical doctor/advance practice registered nurse (MD/APRN) in a sample of 165 combat veterans. Using structural equation modeling, results demonstrated that self-stigma was negatively associated with help-seeking intentions from a mental health professional and MD/APRN with small-to-medium effect sizes. Being married was positively associated with help-seeking intentions from a mental health professional and MD/APRN with small effect sizes. History of previous mental health care engagement was positively associated with help-seeking intentions from a mental health professional with a medium effect size, but unrelated to help-seeking intentions from a MD/APRN. Anticipated enacted stigma from any source, PTS, and greater perceived likelihood of deploying again were unrelated to help-seeking intentions from a mental health professional and MD/APRN. Implications for interventions aimed at decreasing self-stigma and increasing intention to seek help are discussed. © 2013 International Society for Traumatic Stress Studies.


Greish K.,University of Utah
Methods in molecular biology (Clifton, N.J.) | Year: 2010

Effective cancer therapy remains one of the most challenging tasks to the scientific community, with little advancement on overall cancer survival landscape during the last two decades. A major limitation inherent to most conventional anticancer chemotherapeutic agents is their lack of tumor selectivity. One way to achieve selective drug targeting to solid tumors is to exploit abnormalities of tumor vasculature, namely hypervascularization, aberrant vascular architecture, extensive production of vascular permeability factors stimulating extravasation within tumor tissues, and lack of lymphatic drainage. Due to their large size, nano-sized macromolecular anticancer drugs administered intravenously (i.v.) escape renal clearance. Being unable to penetrate through tight endothelial junctions of normal blood vessels, their concentration builds up in the plasma rendering them long plasma half-life. More importantly, they can selectively extravasate in tumor tissues due to its abnormal vascular nature. Overtime the tumor concentration will build up reaching several folds higher than that of the plasma due to lack of efficient lymphatic drainage in solid tumor, an ideal application for EPR-based selective anticancer nanotherapy. Indeed, this selective high local concentration of nano-sized anticancer drugs in tumor tissues has proven superior in therapeutic effect with minimal side effects in both preclinical and clinical settings.


Engeberg E.D.,University of Akron | Meek S.G.,University of Utah
IEEE/ASME Transactions on Mechatronics | Year: 2013

Adaptive sliding mode and integral sliding mode grasped object slip prevention controllers are implemented for a prosthetic hand and compared to a proportional derivative shear force feedback slip prevention controller as well as a sliding mode controller without slip prevention capabilities. Slip of grasped objects is detected by band-pass filtering the shear force derivative to amplify high frequency vibrations that occur as the grasped object slides relative to the fingers. The integral sliding mode slip prevention controller provides a robust design framework for slip prevention while addressing the issue of reducing the amount of deformation that the grasped object experiences to prevent slip. Averaged results from bench top experiments show that the integral sliding mode slip prevention controller produces the least amount of deformation to the grasped object while simultaneously preventing the object from being dropped. © 1996-2012 IEEE.


The 1918 Influenza Pandemic is used as a natural experiment to test the Fetal Origins Hypothesis. This hypothesis states that individual health as well as socioeconomic outcomes, such as educational attainment, employment status, and wages, are affected by the health of that individual while in utero. Repeated cross sections from the Pesquisa Mensal de Emprego (PME), a labor market survey from Brazil, are used to test this hypothesis. I find evidence to support the Fetal Origins Hypothesis. In particular, compared to individuals born in the few years surrounding the Influenza Pandemic, those who were in utero during the pandemic are less likely to be college educated, be employed, have formal employment, or know how to read and have fewer years of schooling and a lower hourly wage. These results underscore the importance of fetal health especially in developing countries. Copyright © 2009 John Wiley & Sons, Ltd.


Yan X.,Zhejiang University | Cook T.R.,State University of New York at Buffalo | Wang P.,Zhejiang University | Huang F.,Zhejiang University | Stang P.J.,University of Utah
Nature Chemistry | Year: 2015

Light-emitting materials, especially those with tunable wavelengths, attract considerable attention for applications in optoelectronic devices, fluorescent probes, sensors and so on. Many species evaluated for these purposes either emit as a dilute solution or on aggregation, with the former often self-quenching at high concentrations, and the latter falling dark when aggregation is disrupted. Here we preserve emissive behaviour at both low-and high-concentration regimes for two discrete supramolecular coordination complexes (SCCs). These tetragonal prismatic SCCs are self-assembled on mixing a metal acceptor, Pt(PEt 3) 2 (OSO 2 CF 3) 2, with two organic donors, a pyridyl-decorated tetraphenylethylene and one of two benzene dicarboxylate species. The rigid organization of these fluorescence-active ligands imparts an emissive behaviour to dilute solutions of the resulting assemblies. Furthermore, on aggregation the prisms exhibit variable-wavelength visible-light emission, including rare white-light emission in tetrahydrofuran. The favourable photophysical properties and solvent-dependent aggregation behaviour provide a means to tune emission wavelengths. © 2015 Macmillan Publishers Limited.


Simons J.,University of Utah
Chemical Physics Letters | Year: 2010

This Letter reviews efforts made to elucidate the mechanism by which electron-capture and electron-transfer dissociation bond cleavages occur in mass spectrometry. The primary issues include where in the parent ion the electron initially attaches, whether the energy released in this initial electron-capture step is key to determining which bonds will cleave, whether the electron can migrate from the site to which it initially attaches to other sites in the parent ion, and, if so, over what distances and at what rates, and why, in polypeptides, one finds disulfide and N-Cα bond cleavage primarily. © 2009 Elsevier B.V. All rights reserved.


O'Connell R.M.,University of Utah | Baltimore D.,California Institute of Technology
Current Topics in Developmental Biology | Year: 2012

Hematopoiesis is a dynamic and highly complex developmental process that gives rise to a multitude of the cell types that circulate in the blood of multicellular organisms. These cells provide tissues with oxygen, guard against infection, prevent bleeding by clotting, and mediate inflammatory reactions. Because the hematopoietic system plays such a central role in human diseases such as infections, cancer, autoimmunity, and anemia, it has been intensely studied for more than a century. This scrutiny has helped to shape many of the developmental paradigms that exist today and has identified specific protein factors that serve as master regulators of blood cell lineage specification. Despite this progress, many aspects of blood cell development remain obscure, suggesting that novel layers of regulation must exist. Consequently, the emergence of regulatory noncoding RNAs, such as the microRNAs (miRNAs), is beginning to provide new insights into the molecular control networks underlying hematopoiesis and diseases that stem from aberrations in this process. This review will discuss how miRNAs fit into our current understanding of hematopoietic development in mammals and how breakdowns in these pathways can trigger disease. © 2012 Elsevier Inc.


Silver R.M.,University of Utah
Obstetrics and Gynecology | Year: 2015

Placental disorders such as placenta previa, placenta accreta, and vasa previa are all associated with vaginal bleeding in the second half of pregnancy. They are also important causes of serious fetal and maternal morbidity and even mortality. Moreover, the rates of previa and accreta are increasing, probably as a result of increasing rates of cesarean delivery, maternal age, and assisted reproductive technology. The routine use of obstetric ultrasonography as well as improving ultrasonographic technology allows for the antenatal diagnosis of these conditions. In turn, antenatal diagnosis facilitates optimal obstetric management. This review emphasizes an evidence-based approach to the clinical management of pregnancies with these conditions as well as highlights important knowledge gaps. © 2015 by The American College of Obstetricians and Gynecologists.


Irmis R.B.,University of Utah
Earth and Environmental Science Transactions of the Royal Society of Edinburgh | Year: 2010

Many hypotheses have been proposed for the rise of dinosaurs, but their early diversification remains poorly understood. This paper examines the occurrences, species diversity and abundance of early dinosaurs at both regional and global scales to determine patterns of their early evolutionary history. Four main patterns are clear: (1) sauropodomorph dinosaurs became abundant during the late Norian-Rhaetian of Gondwana and Europe; (2) Triassic dinosaurs of North America have low species diversity and abundance until the beginning of the Jurassic; (3) sauropodomorphs and ornithischians are absent in the Triassic of North America; and (4) ornithischian dinosaurs maintain low species diversity, relative abundance and small body size until the Early Jurassic. No one hypothesis fully explains these data. There is no evidence for a Carnian-Norian extinction event, but sauropodomorphs did become abundant during the Norian in some assemblages. No clear connection exists between palaeoenvironment and early dinosaur diversity, but environmental stress at the Triassic-Jurassic boundary is consistent with changes in North American dinosaur assemblages. Elevated growth rates in dinosaurs are consistent with the gradual phyletic increase in body size. This study demonstrates that early dinosaur diversification was a complex process that was geographically diachronous and probably had several causes. © 2011 The Royal Society of Edinburgh.


Hawkes K.,University of Utah
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

In the first paper to present formal theory explaining that senescence is a consequence of natural selection, W. D. Hamilton concluded that human postmenopausal longevity results from the contributions of ancestral grandmothers to the reproduction of their relatives.Agrandmother hypothesis, subsequently elaborated with additional lines of evidence, helps explain both exceptional longevity and additional features of life history that distinguish humans from the other great apes. However, some of the variation observed in aging rates seems inconsistent with the tradeoffs between current and future reproduction identified by theory. In humans and chimpanzees, our nearest living relatives, individuals whobear offspring at faster rates do not cease bearing sooner. They continue to be fertile longer instead. Furthermore, within both species, groups with lower overall mortality rates have faster rates of increase in death risk with advancing age. These apparent contradictions to the expected life history tradeoffs likely result from heterogeneity in frailty among individuals. Whereas robust and frail alike must allocate investments between current and future reproduction, the more robust can afford more of both. This heterogeneity, combined with evolutionary tradeoffs and the key role of ancestral grandmothers they identify, helps explain aspects of human aging that increasingly concern us all.


Formosa T.,University of Utah
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2012

FACT is a roughly 180. kDa heterodimeric protein complex important for managing the properties of chromatin in eukaryotic cells. Chromatin is a repressive barrier that plays an important role in protecting genomic DNA and regulating access to it. This barrier must be temporarily removed during transcription, replication, and repair, but it also must be rapidly restored to the original state afterwards. Further, the properties of chromatin are dynamic and must be adjusted as conditions dictate. FACT was identified as a factor that destabilizes nucleosomes in vitro, but it has now also been implicated as a central factor in the deposition of histones to form nucleosomes, as an exchange factor that swaps the histones within existing nucleosomes for variant forms, and as a tether that prevents histones from being displaced by the passage of RNA polymerases during transcription. FACT therefore plays central roles in building, maintaining, adjusting, and overcoming the chromatin barrier. This review summarizes recent results that have begun to reveal how FACT can promote what appear to be contradictory goals, using a simple set of binding activities to both enhance and diminish the stability of nucleosomes. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly. © 2011 Elsevier B.V.


Tolman K.G.,University of Utah
Expert Opinion on Drug Safety | Year: 2011

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) has reached epidemic proportions. Many new therapies have emerged, including thiazolidinediones (TZDs), selective agonists of PPAR-γ, now used as both primary and add-on therapies. Given that T2DM is a lifetime disease, there is a need for assurance that new drugs are both safe and effective. Recent concern about the cardiovascular safety of one of the new drugs, rosiglitazone, is the stimulus for this review. Areas covered: The safety of pioglitazone and rosiglitazone under the headings of liver safety, cardiovascular safety, fluid retention, weight gain and bone fractures is reviewed based on a PubMed search of the years 1997 through June 2010. This review also describes the magnitude of the risks of the TZDs and provides a recommendation on the use of TZDs. Expert opinion: Liver safety is no longer an issue with the TZDs. There are no significant differences between rosiglitazone and pioglitazone in fluid retention, weight gain and bone fractures. However, pioglitazone tends to be cardioprotective while rosiglitazone is cardiotoxic. There is no current justification for prescribing rosiglitazone. © 2011 Informa UK, Ltd.


Bhardwaj A.,Thomas Jefferson University | Casjens S.R.,University of Utah | Cingolani G.,Thomas Jefferson University
Acta Crystallographica Section D: Biological Crystallography | Year: 2014

Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identified in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, evidence is provided that an MiCRU can be inserted in frame inside the gp26 helical core to generate a rationally extended fiber (gp26-2M) which, like gp26, retains a trimeric quaternary structure in solution. The 2.7 Å resolution crystal structure of this engineered fiber, which measures ∼320 Å in length and is only 20-35 Å wide, was determined. This structure, the longest for a trimeric protein fiber to be determined to such a high resolution, reveals the architecture of 22 consecutive trimerization heptads and provides a framework to decipher the structural determinants for protein fiber assembly, stability and flexibility. © 2014 International Union of Crystallography.


Minteer S.D.,University of Utah
Topics in Catalysis | Year: 2012

This review details the use of nanomaterials to improve bioelectrocatalysis for biosensor and biological fuel cell applications. Different types of bioelectrocatalysts are described as well as different types of nanomaterials for improving the rate of bioelectrocatalysis, as well as the active surface area of the electrodes. © Springer Science+Business Media New York 2012.


Jiang H.,Florida International University | Ramirez E.M.,University of Utah
Journal of Climate | Year: 2013

Rainfall and convective properties of tropical cyclones (TCs) are statistically quantified for different TC intensity change categories by using Tropical Rainfall Measuring Mission (TRMM) data from December 1997 to December 2008. Four 24-h future intensity change categories are defined: rapidly intensifying (RI), slowly intensifying, neutral, and weakening. It is found that RI storms always have a larger raining area and total volumetric rain in the inner core. The maximum convective intensity in the inner core is not necessarily more intense prior to undergoing an RI episode than a slowly intensifying, neutral, or weakening episode. Instead, a minimum threshold of raining area, total volumetric rain, and convective intensity in the inner core is determined from the RI cases examined in this study. The following necessary conditions for RI are found in the inner core: total raining area. > 3000km2, total volumetric rain. > 5000mmh-1km2, maximum nearsurface radar reflectivity. > 40 dBZ, maximum 20-dBZ (40 dBZ) echo height. > 8 (4) km, minimum 85-GHz polarization-corrected brightness temperature (PCT) , < 235K, and minimum 10.8-mm brightness temperature , < 220K. To the extent that these thresholds represent all RI cases, they should be of value to forecasters for ruling out RI. This study finds that total lightning activities in the inner core (outer rainband) have a negative (positive) relationship with storm intensification. © 2013 American Meteorological Society.


Vargo D.,University of Utah
American Journal of Surgery | Year: 2012

Background: Wound infections continue to be an issue in abdominal surgery. Tissue perfusion may be a contributing factor. Negative pressure application may have promise in decreasing wound complication. Method: A retrospective review of prospectively collected data in patients with high-risk abdominal wounds was undertaken. Comorbidities, risk factors for infection, wound classification, and wound outcomes were all evaluated. The primary outcome measure was wound infection rate. Secondary outcomes included device safety and overall surgical site complication rate. Results: Thirty patients were identified who had skin flaps in whom negative pressure was used. Negative pressure was applied for an average of 5.6 days (range, 5-7 days). No patient developed ischemia or necrosis of the skin flaps. No wound infections were identified. The overall wound complication rate was 3%. The comparable historical control wound complication rate was 20%, and χ2 analysis showed a statistically significant decrease in the infection rate with negative-pressure wound therapy (P <.05). Conclusions: Negative-pressure wound therapy applied to a closed, high-risk surgical wound is safe, with no evidence of skin necrosis and decreased wound infection rate. © 2012 Elsevier Inc.


Tipple B.J.,University of Utah | Pagani M.,Yale University
Geochimica et Cosmochimica Acta | Year: 2013

Local climate and environment broadly affect the deuterium/hydrogen (D/H) ratios of plant materials, however the degree to which an individual plant's leaf waxes D/H ratios are affected by these parameters remains in question. Understanding these issues is particularly important in order to reconstruct past floral transitions and changes in the paleohydrologic cycle. For this study, we sampled five co-occurring tree species, Acer rubrum, Platanus occidentalis, Juniperus virginiana, Pinus taeda, and Pinus strobus and soils at forty sites along the East Coast of the US, from Florida to Maine. Hydrogen isotopic compositions of leaf wax n-alkanes, stem and surface waters were analyzed and compared against high-resolution temperature, precipitation, relative humidity, and vapor pressure deficit data to determine environmental controls on isotopic composition.Our results demonstrate that each tree species produce a unique distribution of n-alkanes with distinct chain length pattern. Average n-alkane chain lengths recovered from soils, A. rubrum, and J. virginiana leaves show significant correlations with mean annual temperature. δD values of A. rubrum leaf n-alkanes were strongly correlated to modeled mean annual precipitation δD values and other climate parameters related to latitude (i.e. temperature, relative humidity, vapor pressure deficit), while the δD values of J. virginiana n-alkanes were not. Differences in correspondence may reflect the timing of leaf wax synthesis between the two species. Further, soil n-alkane D/H compositions were strongly correlated to modeled mean annual precipitation δD values, while the apparent hydrogen isotopic fractionation was not. These findings indicate that the isotope ratio of n-alkanes from soils in Eastern North American forests and similar ecosystems likely represents a time-averaged value that smooth out the environmental influence any one plant experiences. © 2012 Elsevier Ltd.


Weil D.,University of Paris Descartes | Hollien J.,University of Utah
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2013

Localization of both mRNAs and mRNA decay factors to internal membranes of eukaryotic cells provides a means of coordinately regulating mRNAs with common functions as well as coupling organelle function to mRNA turnover. The classic mechanism of mRNA localization to membranes is the signal sequence-dependent targeting of mRNAs encoding membrane and secreted proteins to the cytoplasmic surface of the endoplasmic reticulum. More recently, however, mRNAs encoding proteins with cytosolic or nuclear functions have been found associated with various organelles, in many cases through unknown mechanisms. Furthermore, there are several types of RNA granules, many of which are sites of mRNA degradation; these are frequently found associated with membrane-bound organelles such as endosomes and mitochondria. In this review we summarize recent findings that link organelle function and mRNA localization to mRNA decay. This article is part of a Special Issue entitled: RNA Decay mechanisms. © 2013 Elsevier B.V.


Sundquist W.I.,University of Utah | Krausslich H.-G.,University of Heidelberg
Cold Spring Harbor Perspectives in Medicine | Year: 2012

A defining property of retroviruses is their ability to assemble into particles that can leave producer cells and spread infection to susceptible cells and hosts. Virion morphogenesis can be divided into three stages: assembly, wherein the virion is created and essential components are packaged; budding, wherein the virion crosses the plasma membrane and obtains its lipid envelope; and maturation, wherein the virion changes structure and becomes infectious. All of these stages are coordinated by the Gag polyprotein and its proteolytic maturation products, which function as the major structural proteins of the virus. Here, we review our current understanding of the mechanisms of HIV-1 assembly, budding, and maturation, starting with a general overview and then providing detailed descriptions of each of the different stages of virion morphogenesis. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.


Kohan D.E.,University of Utah
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2013

Over 26,000 manuscripts have been published dealing with endothelins since their discovery 25 years ago. These peptides, and particularly endothelin-1 (ET-1), are expressed by, bind to, and act on virtually every cell type in the body, influencing multiple biological functions. Among these actions, the effects of ET-1 on arterial pressure and volume homeostasis have been most extensively studied. While ET-1 modulates arterial pressure through regulation of multiple organ systems, the peptide's actions in the kidney in general, and the collecting duct in particular, are of unique importance. The collecting duct produces large amounts of ET-1 that bind in an autocrine manner to endothelin A and B receptors, causing inhibition of Na+ and water reabsorption; absence of collecting duct ET-1 or its receptors is associated with marked salt-sensitive hypertension. Collecting duct ET-1 production is stimulated by Na+ and water loading through local mechanisms that include sensing of salt and other solute delivery as well as shear stress. Thus the collecting duct ET-1 system exists, at least in part, to detect alterations in, and maintain homeostasis for, extracellular fluid volume. Derangements in collecting duct ET-1 production may contribute to the pathogenesis of genetic hypertension. Blockade of endothelin receptors causes fluid retention due, in large part, to inhibition of the action of ET-1 in the collecting duct; this side effect has substantially limited the clinical utility of this class of drugs. Herein, the biology of the collecting duct ET-1 system is reviewed, with particular emphasis on key issues and questions that need addressing. © 2013 the American Physiological Society.


Chubukov A.V.,University of Wisconsin - Madison | Starykh O.A.,University of Utah
Physical Review Letters | Year: 2013

We analyze instabilities of the collinear up-up-down state of a two-dimensional quantum spin-S spatially anisotropic triangular lattice antiferromagnet in a magnetic field. We find, within the large-S approximation, that near the end point of the plateau, the collinear state becomes unstable due to the condensation of two-magnon bound pairs rather than single magnons. The two-magnon instability leads to a novel two-dimensional vector chiral phase with alternating spin currents but no magnetic order in the direction transverse to the field. This phase breaks a discrete Z2 symmetry but preserves a continuous U(1) one of rotations about the field axis. It possesses orbital antiferromagnetism and displays a magnetoelectric effect. © 2013 American Physical Society.


Mace G.G.,University of Utah
Journal of Geophysical Research: Atmospheres | Year: 2010

Annually averaged cloud properties, cloud radiative effects, and cloud radiative heating from 20° × 20° latitude-longitude regions in the Southern Ocean (50°S, 135°W) and the North Atlantic (55°N, 25°W) are compared using quantities derived from measurements collected by active and passive remote sensors in the NASA A-Train. The algorithm suite used to infer cloud properties along the nadir track of the CloudSat and CALIPSO satellites takes input from the cloud boundaries from the merged active remote sensors, radar reflectivity from CloudSat, liquid water path derived from the Advanced Microwave Scanning Radiometer on Aqua, optical depth derived from the Moderate Resolution Imaging Spectroradiometer on Aqua, and top-of-atmosphere (TOA) fluxes measured by the Clouds and the Earth's Radiant Energy System. Errors in annually averaged cloud radiative effect are estimated to range from approximately 5 to 10 W m-2 and heating rate uncertainties range from 0.5 to 2 K day-1. The study regions demonstrate a high degree of similarity in cloud occurrence statistics, in cloud properties, and in the radiative effects of the clouds. Both regions are dominated by a background state of boundary layer clouds (mean liquid water path ∼150 g m -2). Boundary layer clouds and cirrus (mean ice water path ∼100 g m-2) occurring either alone or together amount to approximately 75% of all clouds. Deeper frontal clouds amount to 10%-12% of the coverage. A strong net TOA cooling effect is partitioned between solar cooling of the surface and IR cooling of the atmosphere that is dominated by the ubiquitous boundary layer clouds. It is shown that regimes inferred according to their cloud top pressure and optical depth are often dominated by multiple hydrometeor layers and therefore defy simple classification. Because of this vertical distribution, hydrometeor-induced heating is distributed within the atmosphere in a different way than would be inferred from passive remote-sensing data considered alone. Copyright 2010 by the American Geophysical Union.


Condic M.L.,University of Utah
Journal of Medicine and Philosophy (United Kingdom) | Year: 2016

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., "life support") that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. © 2016 The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved.


Simons J.,University of Utah
Annual Review of Physical Chemistry | Year: 2011

Although this review provides references to tabulations of molecular electron affinities, primarily it focuses on explaining why theory plays an important role in understanding the behavior of anions, explaining the challenges that anions pose to theory, making connections between the theories used to compute electron affinities and the potentials (e.g., charge-dipole, charge-quadrupole, valence attraction and exchange repulsion, dispersion, and polarization) that govern the electron-molecule interaction, and discussing how species with negative electron affinities may possess metastable anion states and how such states should be treated. In addition to references to published literature, many links are given to websites of practicing theoretical chemists who study molecular anions; these links (which appear in boldface) offer the reader a broad avenue to access much more information about molecular anions than can be covered in a review or even through conventional literature sources. © 2011 by Annual Reviews. All rights reserved.


Vanderslice J.,University of Utah
American Journal of Public Health | Year: 2011

Potable drinking water is essential to public health; however, few studies have investigated income or racial disparities in water infrastructure or drinking water quality. There were many case reports documenting a lack of piped water or serious water quality problems in low income and minority communities, including tribal lands, Alaskan Native villages, colonias along the United States-Mexico border, and small communities in agricultural areas. Only 3 studies compared the demographic characteristics of communities by the quality of their drinking water, and the results were mixed in these studies. Further assessments were hampered by difficulties linking specific water systems to the sociodemographic characteristics of communities, as well as little information about how well water systems operated and the effectiveness of governmental oversight.


Pietromonaco P.R.,University of Massachusetts Amherst | Uchino B.,University of Utah | Schetter C.D.,University of California at Los Angeles
Health Psychology | Year: 2013

Objectives: Health psychology has contributed significantly to understanding the link between psychological factors and health and well-being, but it has not often incorporated advances in relationship science into hypothesis generation and study design. We present one example of a theoretical model, following from a major relationship theory (attachment theory) that integrates relationship constructs and processes with biopsychosocial processes and health outcomes. Method: We briefly describe attachment theory and present a general framework linking it to dyadic relationship processes (relationship behaviors, mediators, and outcomes) and health processes (physiology, affective states, health behavior, and health outcomes). We discuss the utility of the model for research in several health domains (e.g., self regulation of health behavior, pain, chronic disease) and its implications for interventions and future research. Results: This framework revealed important gaps in knowledge about relationships and health. Future work in this area will benefit from taking into account individual differences in attachment, adopting a more explicit dyadic approach, examining more integrated models that test for mediating processes, and incorporating a broader range of relationship constructs that have implications for health. Conclusions: A theoretical framework for studying health that is based in relationship science can accelerate progress by generating new research directions designed to pinpoint the mechanisms through which close relationships promote or undermine health. Furthermore, this knowledge can be applied to develop more effective interventions to help individuals and their relationship partners with healthrelated challenges. © 2013 American Psychological Association.


Pagliarini D.J.,University of Wisconsin - Madison | Rutter J.,University of Utah
Genes and Development | Year: 2013

Stemming from the pioneering studies of bioenergetics in the 1950s, 1960s, and 1970s, mitochondria have become ingrained in the collective psyche of scientists as the "powerhouses" of the cell. While this remains a worthy moniker, more recent efforts have revealed that these organelles are home to a vast array of metabolic and signaling processes and possess a proteomic landscape that is both highly varied and largely uncharted. As mitochondrial dysfunction is increasingly being implicated in a spectrum of human diseases, it is imperative that we construct a more complete framework of these organelles by systematically defining the functions of their component parts. Powerful new approaches in biochemistry and systems biology are helping to fill in the gaps. © 2013 Pagliarini and Rutter.


Gordon Smith A.,University of Utah
Journal of the Peripheral Nervous System | Year: 2012

Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case-control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT-associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies. © 2012 Peripheral Nerve Society.


Stringfellow G.B.,University of Utah
Journal of Crystal Growth | Year: 2010

Effects due to phase separation in InGaN have been identified as having major effects on the performance of devices, in particular light-emitting diodes (LEDs) and injection lasers. However, the complexity of the various materials phenomena that can occur has led to a great deal of recent confusion. Much of this confusion can be eliminated by considering the experimentally measured materials properties in the context of the set of physical phenomena occurring during epitaxial growth, including coupling that exists between the various effects. Spinodal decomposition is expected to produce phase separation due to the miscibility gap in InGaN alloys. However, the actual occurrence of this phenomenon has been disputed due to the complexity of real systems. For example, the region of solid immiscibility for InGaN is strongly dependent on elastic strain. In addition, the strain, itself, affects properties such as the bandgap energy. Complicating the analysis of these phenomena is that the solid composition can be affected by elastic strain due to the well-known thermodynamic phenomenon of "compositional pulling". An additional factor must be considered if the experimentally observed phenomena are to be understood. Thin, lattice mismatched epitaxial layers are coherent with the substrate (or underlying layer). Thus, the actual growth process for the formation of lattice mismatched layers, namely the Stranski-Krastanov (S-K) formation of islands, must be included in any realistic growth model. By considering all the phenomena together, including the coupling between them, it becomes clear that several separate mechanisms exist for phase separation. The focus of this paper is the analysis of the thin (2-3 nm), coherent InGaN layers used in the quantum well structures used for virtually all LEDs and lasers produced by the S-K mechanism. By considering these coupled phenomena together it is possible to arrive at a coherent interpretation of the various materials properties measured using techniques such as high resolution transmission electron microscopy, X-ray diffraction, and optical techniques as well as the device characteristics. © 2009 Elsevier B.V. All rights reserved.


Weiss R.L.,University of Utah
American Journal of Clinical Pathology | Year: 2012

"High complexity" clinical laboratories are approved under the Clinical Laboratory Improvement Amendments to develop, validate, and offer a laboratory-developed test (LDT) for clinical use. The Food and Drug Administration considers LDTs to be medical devices under their regulatory jurisdiction, and that at least certain LDTs should be subject to greater regulatory scrutiny. This review describes the current regulatory framework for LDTs and suggests ways in which to appropriately enhance this framework. © American Society for Clinical Pathology.


The demographic shift towards an older population increases the public health burden. Two conditions, commonly occurring together, that contribute to this burden are hypertension and diabetes mellitus. Effective blood pressure (BP) control is particularly important in this patient population, with a recommended BP goal of <130/80mmHg. Most of these patients will require treatment with a combination of antihypertensive agents to reach this goal. Polypharmacy can be defined as the use of two or more medications, and it is commonly seen in this patient population. The risks of polypharmacy and the potential for inappropriate therapy must be considered and balanced against the possible benefits of multiple drug therapies. An optimal approach to reducing the risks and maximizing the benefits of polypharmacy should include regular reviews of patients medication lists, which can be changed to include, where appropriate, combination therapy and the use of single-pill combinations. Combination therapy can achieve greater BP reductions than monotherapy and can also enhance the safety and tolerability of pharmacotherapy. The safety and efficacy of numerous antihypertensive combinations in elderly patients have been demonstrated in a number of clinical trials. Single-pill formulations can simplify the medication regimen, and specific combinations can offer further benefits, such as enhanced reduction of macrovascular and microvascular complications, independent of BP reductions. Rational combination therapy can maximize BP control along with glycaemic control and help maximize the benefits of polypharmacy on outcomes in elderly patients with hypertension and co-morbid diabetes. © 2010 Adis Data Information BV. All rights reserved.


Rodgers G.M.,University of Utah
American Journal of Hematology | Year: 2012

The use of prothrombin complex concentrates (PCCs), a heterogeneous combination of coagulation factors and counterbalancing inhibitor components, has broadened in recent years beyond single-factor replacement in conditions such as hemophilia B, to encompass emergency reversal of anticoagulation secondary to oral vitamin K antagonists, ie, warfarin therapy. PCCs also have been studied in other bleeding disorders, such as surgery-related and trauma-related bleeding. This review provides an updated examination of the differences among PCC formulations, their potential role in the management of bleeding disorders, and the primary safety issues affecting their use. © 2012 Wiley Periodicals, Inc..


Chen F.-M.,University of Utah
Journal of High Energy Physics | Year: 2010

We define a 3-algebra with structure constants being symmetric in the first two indices. We also introduce an invariant anti-symmetric tensor into this 3-algebra and call it a symplectic 3-algebra. The general N = 5 superconformal Chern-Simons-matter (CSM) theory with SO(5) R-symmetry in three dimensions is constructed by using this algebraic structure. We demonstrate that the supersymmetry can be enhanced to N = 6 if the sympelctic 3-algebra and the fields are decomposed in a proper fashion. By specifying the 3-brackets, some presently known N = 5,6 superconformal theories are described in terms of this unified 3-algebraic framework. These include the N = 5, Sp(2N) ×O(M) CSM theory with SO(5) R-symmetry, the N = 6, Sp(2N) × U(1) CSM theory with SU(4) R-symmetry, as well as the ABJM theory as a special case of U(M) × U(N) theory with SU(4) R-symmetry. © 2010 SISSA, Trieste, Italy.


Lawson S.,University of Utah
Journal of Information Technology and Politics | Year: 2013

Cybersecurity proponents often rely on cyber-doom scenarios as a key tactic for calling attention to prospective cyberthreats. This article critically examines cyber-doom scenarios by placing them in a larger historical context, assessing how realistic they are, and drawing out the policy implications of relying on such tales. It draws from relevant research in the history of technology, military history, and disaster sociology to examine some of the key assertions and assumptions of cyber-doom scenarios. The article argues that cyber-doom scenarios are the latest manifestation of fears about "technology-out-of-control" in Western societies, that they are unrealistic, and that they encourage the adoption of counterproductive, even dangerous policies. The article concludes by offering alternative principles for the formulation of cybersecurity policy. © 2013 Copyright Taylor & Francis Group, LLC.


Hawkes K.,University of Utah
Human Nature | Year: 2014

Developmental psychologists identify propensities for social engagement in human infants that are less evident in other apes; Sarah Hrdy links these social propensities to novel features of human childrearing. Unlike other ape mothers, humans can bear a new baby before the previous child is independent because they have help. This help alters maternal trade-offs and so imposes new selection pressures on infants and young children to actively engage their caretakers' attention and commitment. Such distinctive childrearing is part of our grandmothering life history. While consequences for other cooperative activities must surely follow, the novel rearing environments set up by helpful grandmothering can explain why natural selection escalated preferences and motivations for interactivity in our lineage in the first place, and why, unlike other aspects of infant development, social sensitivities are not delayed in humans compared with genus Pan. © 2013 Springer Science+Business Media New York.


Zang L.,University of Utah
Accounts of Chemical Research | Year: 2015

ConspectusSelf-assembly of π-conjugate molecules often leads to formation of well-defined nanofibril structures dominated by the columnar π-π stacking between the molecular planes. These nanofibril materials have drawn increasing interest in the research frontiers of nanomaterials and nanotechnology, as the nanofibers demonstrate one-dimensionally enhanced exciton and charge diffusion along the long axis, and present great potential for varying optoelectronic applications, such as sensors, optics, photovoltaics, and photocatalysis. However, poor electrical conductivity remains a technical drawback for these nanomaterials. To address this problem, we have developed a series of nanofiber structures modified with different donor-acceptor (D-A) interfaces that are tunable for maximizing the photoinduced charge separation, thus leading to increase in the electrical conductivity. The D-A interface can be constructed with covalent linker or noncovalent interaction (e.g., hydrophobic interdigitation between alkyl chains). The noncovalent method is generally more flexible for molecular design and solution processing, making it more adaptable to be applied to other fibril nanomaterials such as carbon nanotubes. In this Account, we will discuss our recent discoveries in these research fields, aiming to provide deep insight into the enabling photoconductivity of nanofibril materials, and the dependence on interface structure.The photoconductivity generated with the nanofibril material is proportional to the charge carriers density, which in turn is determined by the kinetics balance of the three competitive charge transfer processes: (1) the photoinduced electron transfer from D to A (also referred to as exciton dissociation), generating majority charge carrier located in the nanofiber; (2) the back electron transfer; and (3) the charge delocalization along the nanofiber mediated by the π-π stacking interaction. The relative rates of these charge transfer processes can be tuned by the molecular structure and nanoscale interface engineering. As a result, maximal photoconductivity can be achieved for different D-A nanofibril composites. The photoconductive nanomaterials thus obtained demonstrate unique features and functions when employed in photochemiresistor sensors, photovoltaics and photocatalysis, all taking advantages of the large, open interface of nanofibril structure. Upon deposition onto a substrate, the intertwined nanofibers form networks with porosity in nanometer scale. The porous structure enables three-dimensional diffusion of molecules (analytes in sensor or reactants in catalysis), facilitating the interfacial chemical interactions. For carbon nanotubes, the completely exposed π-conjugation facilitates the surface modification through π-π stacking in conjunction with D-A interaction. Depending on the electronic energy levels of D and A parts, appropriate band alignment can be achieved, thus producing an electric field across the interface. Presence of such an electric field enhances the charge separation, which may lead to design of new type of photovoltaic system using carbon nanotube composite. © 2015 American Chemical Society.


Kumar V.,University of Utah
IEEE Transactions on Image Processing | Year: 2013

Grain size statistics, texture, and grain boundary distribution are microstructural characteristics that greatly influence materials properties. These characteristics can be derived from an orientation map obtained using orientation imaging microscopy (OIM) techniques. The OIM techniques are generally performed using a transmission electron microscopy (TEM) for nanomaterials. Although some of these techniques have limited applicability in certain situations, others have limited availability because of external hardware required. In this paper, an automated method to generate orientation maps using convergence beam electron diffraction patterns obtained in a conventional TEM setup is presented. This method is based upon dynamical diffraction theory that describes electron diffraction more accurately as compared with kinematical theory used by several existing OIM techniques. In addition, the method of this paper uses wide angle convergent beam electron diffraction for performing OIM. It is shown in this paper that the use of the wide angle convergent electron beam provides additional information that is not available otherwise. Together, the presented method exploits the additional information and combines it with the calculations from the dynamical theory to provide accurate orientation maps in a conventional TEM setup. The automated method of this paper is applied to a platinum thin film sample. The presented method correctly identified the texture preference in the sample. © 1992-2012 IEEE.


Renshaw S.A.,University of Sheffield | Trede N.S.,University of Utah
DMM Disease Models and Mechanisms | Year: 2012

Since its first splash 30 years ago, the use of the zebrafish model has been extended from a tool for genetic dissection of early vertebrate development to the functional interrogation of organogenesis and disease processes such as infection and cancer. In particular, there is recent and growing attention in the scientific community directed at the immune systems of zebrafish. This development is based on the ability to image cell movements and organogenesis in an entire vertebrate organism, complemented by increasing recognition that zebrafish and vertebrate immunity have many aspects in common. Here, we review zebrafish immunity with a particular focus on recent studies that exploit the unique genetic and in vivo imaging advantages available for this organism. These unique advantages are driving forward our study of vertebrate immunity in general, with important consequences for the understanding of mammalian immune function and its role in disease pathogenesis. © 2012. Published by The Company of Biologists Ltd.


Thomas Fletcher P.,University of Utah
International Journal of Computer Vision | Year: 2013

This paper develops the theory of geodesic regression and least-squares estimation on Riemannian manifolds. Geodesic regression is a method for finding the relationship between a real-valued independent variable and a manifold-valued dependent random variable, where this relationship is modeled as a geodesic curve on the manifold. Least-squares estimation is formulated intrinsically as a minimization of the sum-of-squared geodesic distances of the data to the estimated model. Geodesic regression is a direct generalization of linear regression to the manifold setting, and it provides a simple parameterization of the estimated relationship as an initial point and velocity, analogous to the intercept and slope. A nonparametric permutation test for determining the significance of the trend is also given. For the case of symmetric spaces, two main theoretical results are established. First, conditions for existence and uniqueness of the least-squares problem are provided. Second, a maximum likelihood criteria is developed for a suitable definition of Gaussian errors on the manifold. While the method can be generally applied to data on any manifold, specific examples are given for a set of synthetically generated rotation data and an application to analyzing shape changes in the corpus callosum due to age. © 2012 Springer Science+Business Media New York.


Fang X.,University of Utah
IEEE Transactions on Knowledge and Data Engineering | Year: 2013

A fundamental challenge for developing a cost-sensitive Naïve Bayes method is how to effectively classify an instance based on the cost-sensitive threshold computed under the assumption of knowing the instance's true classification probabilities and the highly biased estimations of these probabilities by the Naïve Bayes method. To address this challenge, we develop a cost-sensitive Naïve Bayes method from a novel perspective of inferring the order relation (e.g., greater than or equal to, less than) between an instance's true classification probability of belonging to the class of interest and the cost-sensitive threshold. Our method learns and infers the order relation from the training data and classifies the instance based on the inferred order relation. We empirically show that our proposed method significantly outperforms major existing methods for turning Naïve Bayes cost-sensitive through experiments with UCI data sets and a real-world case study. © 1989-2012 IEEE.


Orlandi R.R.,University of Utah
Laryngoscope | Year: 2010

Objectives/Hypothesis: Rhinosinusitis might have many etiologies that lead to a common presentation of inflammation and impaired mucociliary clearance. Anatomic factors were once thought to play a large role in the pathogenesis of rhinosinusitis, and septal deviation was examined in multiple studies with conflicting results. With the more recent appreciation that the development of rhinosinusitis is likely multifactorial, it is appropriate to re-examine possible anatomic etiologies. A systematic analysis of septal deviation and rhinosinusitis was therefore performed to better define this association and describe possible etiologic mechanisms. Examination of a large sample, accomplished through systematically identifying and combining previous studies, may compensate for the several shortcomings of these separate analyses. A systematic analysis was therefore performed to answer the question, is septal deviation associated with rhinosinusitis? Study Design: Systematic analysis of previously published studies. Methods: Following a structured literature search, articles examining the association of septal deviation and rhinosinusitis were analyzed quantitatively and qualitatively. Based on the quantitative results, a septal deviation angle (SDA) cutoff of 10° was chosen for distinguishing positive from negative for septal deviation in the qualitative analysis. Results: Of over 300 references initially identified, 13 articles comprised the basis of this review. Increasing angles of septal deviation were associated with increasing prevalence of rhinosinusitis in multiple studies. Combining the results of five previous studies on this subject demonstrated significant association of septal deviation and rhinosinusitis (P = .0004, χ 2 analysis). The clinical effect was found, however, to be modest with an odds ratio of 1.47. Interestingly, in all studies that examined the laterality of rhinosinusitis associated with septal deviation, inflammation was found bilaterally. Based on the data from this analysis, it appears that many of the previous analyses were insufficiently powered to detect an association between rhinosinusitis and septal deviation. Others failed to find an association by examining subjects with small SDAs. Conclusions: Septal deviation is associated with an increased prevalence of rhinosinusitis, although the impact of this anatomic anomaly is limited. It appears to be one of many possible factors that might lead to the development of rhinosinusitis. © 2010 The American Laryngological, Rhinological and Otological Society, Inc.


Parker C.J.,University of Utah
Current Opinion in Hematology | Year: 2012

Purpose of Review: The aim is to report on recent observations related to the natural history of paroxysmal nocturnal hemoglobinuria (PNH) and to review new therapeutic strategies for controlling the hemolysis of PNH. Recent Findings: This review focuses on studies designed to characterize the long-term outcome of patients with PNH treated with eculizumab and to define the relationship between PNH and bone marrow failure syndromes. New therapeutic strategies aimed at controlling extravascular as well as intravascular hemolysis are also examined. Summary: Long-term safety and efficacy of eculizumab was observed in a large group of patients. Survival for the group was not different from that of a sex-matched and age-matched control group from the general population. Thrombotic complications were rare and deaths due to PNH or complications of therapy were not observed. These studies suggest that patients with clinical PNH who are treated with eculizumab have a benign clinical course. Patients with bone marrow failure who have PNH cells detected by high-sensitivity flow cytometry have aplastic anemia or low-risk myelodysplastic syndrome. For patients with a percentage of PNH cells that is below the threshold for producing laboratory evidence of hemolysis (subclinical PNH), expansion of the clone to a size sufficient to produce clinical PNH is not observed. Approximately 50% of patients with bone marrow failure who have clinical evidence of PNH at presentation will require PNH-specific therapy. Novel reagents that target the alternative pathway of complement C3 convertase are being developed with a goal of inhibiting both the extravascular and the intravascular hemolysis of PNH. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Facelli J.C.,University of Utah
Progress in Nuclear Magnetic Resonance Spectroscopy | Year: 2011

The development of fast and accurate methods to calculate 13C and 1H NMR chemical shifts using purely empirical models provide extremely fast calculations that are useful for high throughput studies. The high speed of chemical shift calculations is achieved using a simple structure description scheme based on individual atoms rather than functional groups. The Torsion Angle Likeliness Obtained from Shift and Sequence Similarity (TALOS) approach is based on the observation that the chemical shift in proteins depends strongly on the local structure. It can predict the backbone angles of 88.5% residues with a standard deviation of 5.5%. The development of effective Density Functional Theory (DFT) methods that include electronic correlation effects has proved to be an important tool in the field of shielding calculations. Using the DFT theory, which scales as N2, it is possible to calculate shieldings in molecular systems of practical interest including electronic correlation effects.


The discovery of non-random chromosome segregation (Figure 1) is discussed from the perspective of what was known in 1965 and 1966. The distinction between daughter, parent, or grandparent strands of DNA was developed in a bacterial system and led to the discovery that multiple copies of DNA elements of bacteria are not distributed randomly with respect to the age of the template strand. Experiments with higher eukaryotic cells demonstrated that during mitosis Mendel's laws were violated; and the initial serendipitous choice of eukaryotic cell system led to the striking example of non-random segregation of parent and grandparent DNA template strands in primary cultures of cells derived from mouse embryos. Attempts to extrapolate these findings to established tissue culture lines demonstrated that the property could be lost. Experiments using plant root tips demonstrated that the phenomenon exists in plants and that it was, at some level, under genetic control. Despite publication in major journals and symposia (Lark et al., 1966, 1967; Lark, 1967, 1969a,b,c) the potential implications of these findings were ignored for several decades. Here we explore possible reasons for the pre-maturity (Stent, 1972) of this discovery. © 2013 Lark.


Carroll D.,University of Utah
Current Gene Therapy | Year: 2011

Zinc-finger nucleases (ZFNs) are emerging as very powerful tools for directed genome modifications. Their key features are: a DNA-binding domain comprised of zinc fingers that can be designed to favor very specific targets; a nonspecific cleavage domain that must dimerize to cut DNA - this requirement enhances specificity and minimizes random cleavage. ZFNs have been shown to be effective in a wide range of organisms and cell types. This article reviews discoveries that led to the development of ZFNs, cites examples of successes in genome engineering, and projects how ZFNs may be used in the future, particularly in applications to humans. © 2011 Bentham Science Publishers Ltd.


Horvath M.P.,University of Utah
Critical Reviews in Biochemistry and Molecular Biology | Year: 2011

Telomere DNA-binding proteins protect the ends of chromosomes in eukaryotes. A subset of these proteins are constructed with one or more OB folds and bind with G+T-rich single-stranded DNA found at the extreme termini. The resulting DNA-OB protein complex interacts with other telomere components to coordinate critical telomere functions of DNA protection and DNA synthesis. While the first crystal and NMR structures readily explained protection of telomere ends, the picture of how single-stranded DNA becomes available to serve as primer and template for synthesis of new telomere DNA is only recently coming into focus. New structures of telomere OB fold proteins alongside insights from genetic and biochemical experiments have made significant contributions towards understanding how protein-binding OB proteins collaborate with DNA-binding OB proteins to recruit telomerase and DNA polymerase for telomere homeostasis. This review surveys telomere OB protein structures alongside highly comparable structures derived from replication protein A (RPA) components, with the goal of providing a molecular context for understanding telomere OB protein evolution and mechanism of action in protection and synthesis of telomere DNA. © 2011 Informa Healthcare USA, Inc.


Alcott T.I.,National Weather Service - NWS | Steenburgh W.J.,University of Utah
Monthly Weather Review | Year: 2013

Although several mountain ranges surround the Great Salt Lake (GSL) of northern Utah, the extent to which orography modifies GSL-effect precipitation remains largely unknown. Here the authors use observational and numerical modeling approaches to examine the influence of orography on the GSL-effect snowstorm of 27 October 2010, which generated 6-10mmof precipitation (snow-water equivalent) in the Salt Lake Valley and up to 30cm of snow in the Wasatch Mountains. The authors find that the primary orographic influences on the event are 1) foehnlike flow over the upstream orography that warms and dries the incipient low-level air mass and reduces precipitation coverage and intensity; 2) orographically forced convergence that extends downstream from the upstream orography, is enhanced by blocking windward of the Promontory Mountains, and affects the structure and evolution of the lake-effect precipitation band; and 3) blocking by the Wasatch and Oquirrh Mountains, which funnels the flow into the Salt Lake Valley, reinforces the thermally driven convergence generated by the GSL, and strongly enhances precipitation. The latter represents a synergistic interaction between lake and downstream orographic processes that is crucial for precipitation development, with a dramatic decrease in precipitation intensity and coverage evident in simulations in which either the lake or the orography are removed. These results help elucidate the spectrum of lake-orographic processes that contribute to lake-effect events and may be broadly applicable to other regions where lake effect precipitation occurs in proximity to complex terrain. © 2013 American Meteorological Society.


Peters C.L.,University of Utah
Journal of Arthroplasty | Year: 2015

Treatment of structural hip disease such as FAI and acetabular dysplasia has increased dramatically over the past decade with the goal of preservation of the native hip joint. A number of patient and disease specific parameters including the amount of underlying hip osteoarthrosis can help predict success with joint preservation surgery. Total hip arthroplasty remains a very good option in young patients who are not ideal candidates for joint preservation surgery. Future developments will help to better identify ideal surgical candidates and improve understanding of the disease processes. © 2015 Elsevier Inc..


Friedman D.I.,University of Texas Southwestern Medical Center | Liu G.T.,University of Pennsylvania | Digre K.B.,University of Utah
Neurology | Year: 2013

The pseudotumor cerebri syndrome (PTCS) may be primary (idiopathic intracranial hypertension) or arise from an identifiable secondary cause. Characterization of typical neuroimaging abnormalities, clarification of normal opening pressure in children, and features distinguishing the syndrome of intracranial hypertension without papilledema from intracranial hypertension with papilledema have furthered our understanding of this disorder. We propose updated diagnostic criteria for PTCS to incorporate advances and insights into the disorder realized over the past 10 years. © 2013 American Academy of Neurology.


Flatt M.,University of Utah
Communications of the ACM | Year: 2012

Sometimes you just have to make a better mousetrap.


Plutynski A.,University of Utah
Journal of Medicine and Philosophy (United Kingdom) | Year: 2012

November 2009's announcement of the USPSTF's recommendations for screening for breast cancer raised a firestorm of objections. Chief among them were that the panel had insufficiently valued patients' lives or allowed cost considerations to influence recommendations. The publicity about the recommendations, however, often either simplified the actual content of the recommendations or bypassed significant methodological issues, which a philosophical examination of both the science behind screening recommendations and their import reveals. In this article, I discuss two of the leading ethical considerations at issue in screening recommendations: respect for patient autonomy and beneficence and then turn to the most significant methodological issues raised by cancer screening: the potential biases that may infect a trial of screening effectiveness, the problem of base rates in communicating risk, and the trade-offs involved in a judgment of screening effectiveness. These issues reach more broadly, into the use of "evidence-based" medicine generally, and have important implications for informed consent. © The Author 2012. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved.


Oderda G.,University of Utah
Pharmacotherapy | Year: 2012

The majority of patients who undergo surgery will require drug therapy for the management of acute postsurgical pain. Effective control of acute postsurgical pain is essential for the patient not only in the short term but also in the long term to prevent the development of chronic pain, which can occur if early acute pain is prolonged. Currently, opioid analgesics are widely used for the management of acute postsurgical pain. Although opioids provide effective postsurgical pain relief, their use is associated with a number of risks, including the development of opioid-related adverse drug events (ORADEs). This review investigates the prevalence of opioid use in the postsurgical setting, the incidence of ORADEs, and the impact of these ORADEs on patient outcomes, length of stay, and costs after common surgeries. According to a national analysis of ORADE incidence, almost 20% of patients treated with opioids experienced an ORADE, with the most common being gastrointestinal effects, central nervous system effects, pruritus, or urinary retention. Studies show that the risk of developing an ORADE is higher in patients receiving higher doses of opioids and in patients undergoing orthopedic or gynecologic surgery compared with patients undergoing general surgery. Elderly patients and those with comorbidities (e.g., obesity, sleep apnea, respiratory disease, urinary disorders) may be particularly vulnerable to ORADE development. Both hospital costs and length of stay are increased in patients with an ORADE versus those without an ORADE. Strategies to reduce the use of opioids after surgery are likely to result in positive outcomes by reducing the incidence of ORADEs and, as a result, reducing treatment costs associated with surgery and improving patient care.


Scott J.R.,University of Utah
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2014

Few studies have focused specifically on the intrapartum management of patients following a prior caesarean delivery. Contemporary assessments and recommendations on attempting vaginal birth after caesarean delivery (VBAC) vary. The actual conduct of labour and delivery of the infant in an uncomplicated trial of labour after caesarean (TOLAC) is similar to the management of a patient without a previous caesarean. Intrapartum management of TOLAC differs primarily in the need for caution with induction of labour in women with an unfavourable cervix, the avoidance of overstimulation with oxytocin augmentation, and surveillance for prompt recognition of the rare case of uterine rupture. © 2013 Royal College of Obstetricians and Gynaecologists.


Dorval A.D.,University of Utah | Grill W.M.,Duke University
Journal of Neurophysiology | Year: 2014

Pathophysiological activity of basal ganglia neurons accompanies the motor symptoms of Parkinson's disease. High-frequency (>90 Hz) deep brain stimulation (DBS) reduces parkinsonian symptoms, but the mechanisms remain unclear. We hypothesize that parkinsonism-associated electrophysiological changes constitute an increase in neuronal firing pattern disorder and a concomitant decrease in information transmission through the ventral basal ganglia, and that effective DBS alleviates symptoms by decreasing neuronal disorder while simultaneously increasing information transfer through the same regions. We tested these hypotheses in the freely behaving, 6-hydroxydopamine-lesioned rat model of hemiparkinsonism. Following the onset of parkinsonism, mean neuronal firing rates were unchanged, despite a significant increase in firing pattern disorder (i.e., neuronal entropy), in both the globus pallidus and substantia nigra pars reticulata. This increase in neuronal entropy was reversed by symptom-alleviating DBS. Whereas increases in signal entropy are most commonly indicative of similar increases in information transmission, directed information through both regions was substantially reduced (>70%) following the onset of parkinsonism. Again, this decrease in information transmission was partially reversed by DBS. Together, these results suggest that the parkinsonian basal ganglia are rife with entropic activity and incapable of functional information transmission. Furthermore, they indicate that symptom-alleviating DBS works by lowering the entropic noise floor, enabling more information-rich signal propagation. In this view, the symptoms of parkinsonism may be more a default mode, normally overridden by healthy basal ganglia information. When that information is abolished by parkinsonian pathophysiology, hypokinetic symptoms emerge. © 2014 the American Physiological Society.


Schoenwolf G.C.,University of Utah
Development Growth and Differentiation | Year: 2013

Publication in international scientific journals provides an unparalleled opportunity for authors to showcase their work. Where authors publish affects how the community values the work. This value directly determines the impact of the work on the field-papers must be read and cited to advance the field, and because the scientific literature is vast, only a subset of the literature is widely read and cited. Moreover, the value placed on the work also affects the authors' scientific reputation and career advancement. Consequently, it is essential that manuscripts receive the recognition they deserve by being published in one of the "best" journals that the scientific findings allow. Several factors determine where a paper is published: how well the topic of the paper fits the scope of the journal, the quality of the study and the manuscript describing it, the advance the paper makes in its field, the importance of the advance, and the extent to which the paper impacts the broader community of science. As scientists, we assume that our papers will be assessed objectively using only well defined scientific standards, but editors and reviewers also view papers subjectively, having biases of what defines a high-quality publication based on Western standards. Therefore, scientists trained in other parts of the world can be significantly disadvantaged in getting their papers published in the best journals. Here, I present concrete suggestions for improving the perception of a paper in the reader's minds, increasing the likelihood that it will get published well. © 2013 Japanese Society of Developmental Biologists.


Kuhn S.,Johannes Gutenberg University Mainz | Rahe P.,University of Utah
Physical Review B - Condensed Matter and Materials Physics | Year: 2014

Noncontact atomic force microscopy (NC-AFM) features the measurement of forces with highest spatial resolution and sensitivity, resolving forces of the order of pico-Newtons with submolecular resolution. However, the measured total force is a mixture composed of various interactions. While some interactions such as electrostatic or magnetic forces can be excluded by a careful design of the experiment, the subtraction of van der Waals forces, which mainly originate from London dispersion interactions between the macroscopic tip shank and the bulk sample, remains a challenge. We present the determination of the inherently present van der Waals forces in total interaction force data from fitting a suitable model, allowing for extraction of the short-range force component. We compare the applicability of several van der Waals models based on experimental interaction data from the calcite(101̄4) surface. The feasibility to fit these models to experimental data is critically discussed. We furthermore introduce criteria to assess the transition point from pure long-range interaction to mixed short- and long-range forces based on the variance of lateral and vertical force data. This determination allows us to extract the short-range interaction forces, which remained a challenge so far in NC-AFM experiments. © 2014 American Physical Society.


Schmandt B.,University of New Mexico | Lin F.-C.,University of Utah
Geophysical Research Letters | Year: 2014

Mantle seismic structure beneath the United States spanning from the active western plate margin to the passive eastern margin was imaged with teleseismic P and S wave traveltime tomography including USArray data up to May 2014. To mitigate artifacts from crustal structure 5-40 s, Rayleigh wave phase velocities were used to create a 3-D starting model. Major features of the final P and S models include two distinct low-velocity anomalies at depths of ~60-300 km beneath the central and northern Appalachians and passive margin. The central Appalachian low-velocity anomaly coincides with Eocene basaltic magmatism, and the northern anomaly is located along the Cretaceous track of the Great Meteor hot spot. At depths of ~300-700 km beneath the central and eastern U.S. large high-velocity anomalies are inferred to be remnants of the Farallon slab that subducted prior to ~40 Ma during the Laramide orogeny. Key Points P wave and S wave mantle tomography spanning the contiguous U.S.Passive margin low-velocity anomalies linked to Cenozoic and Mesozoic volcanismSome Laramide-age slab fragments have yet to sink into the lower mantle ©2014. American Geophysical Union. All Rights Reserved.


The extremely damaging Hurricane Sandy (2012) is noteworthy for the significant track bifurcation among several forecast models approximately 6-7days before landfall. The operational versions of the European Center for Medium-Range Weather Forecasting (ECMWF) and Global Forecast System (GFS) models exemplify this difference over their runs early in Sandy's life cycle, as the former routinely forecast a storm which would make a U.S. landfall, while the latter routinely forecast a track toward the central North Atlantic. This was also generally true of their respective ensemble members. This paper demonstrates that these differences were caused not by resolution or initial condition differences but rather due almost exclusively to choice of cumulus parameterization. Simulations performed with the Weather Research and Forecasting model using an ECMWF-like cumulus parameterization in conjunction with GFS initial conditions yield forecasts whose accuracy is similar to that of ECMWF forecasts at extended time ranges (up to 1 week before landfall). Key Points Global Sandy forecasts are dependent upon choice of cumulus parameterization Disparate tracks can be reproduced using identical initial conditions © 2014. The Authors.


Kramer K.L.,University of Utah
Human Nature | Year: 2014

The evolution of cooperative breeding is complex, and particularly so in humans because many other life history traits likely evolved at the same time. While cooperative childrearing is often presumed ancient, the transition from maternal self-reliance to dependence on allocare leaves no known empirical record. In this paper, an exploratory model is developed that incorporates probable evolutionary changes in birth intervals, juvenile dependence, and dispersal age to predict under what life history conditions mothers are unable to raise children without adult cooperation. The model's outcome variable (net balance) integrates dependent children's production and consumption as a function of varying life history parameters to estimate the investment mothers or others have to spend subsidizing children. Results suggest that maternal-juvenile cooperation can support the early transition toward a reduction in birth intervals, a longer period of juvenile dependence, and having overlapping young. The need for adult cooperation is most evident when birth intervals are short and age at net production is late. Findings suggest that the needs of juveniles would not have been an early selective force for adult cooperation. Rather, an age-graded division of labor and the mutual benefits of maternal-juvenile cooperation could be an important, but overlooked step in the evolution of cooperative breeding. © 2014 Springer Science+Business Media New York.


Shulga Y.V.,McMaster University | Topham M.K.,University of Utah | Epand R.M.,McMaster University
Chemical Reviews | Year: 2011

Diacylglycerol (DAG) is an important lipid that is both an intermediate in lipid biosynthetic pathways and can act as a signaling lipid. Unlike bacteria and yeast, multicellular organisms express more than one, and often several, DGK isoforms that can be grouped by common structural elements into five subfamilies. The DGKs expressed in mammals are the best characterized, and 10 of them have been identified. Most tissues express several different DGK isoforms, and even within the same cell type, more than one DGK isoform can exist. DGKs have been identified in a number of cell compartments, including the nucleus. Their localization within the nucleus is not surprising because it has a phosphatidylinositol cycle that is regulated separately from plasma membrane phosphatidylinositol signaling. The degree of specificity of DGKe for SAG compared with other structurally related forms of DAG with small differences in acyl chain length or degree of unsaturation is relatively modest.


Silver R.,University of Utah
Fertility and Sterility | Year: 2014

Traditionally, the primary outcome of infertility trials has been a positive pregnancy test or a clinically recognized pregnancy. However, parents desire a healthy baby that grows up to be a healthy adult, rather than a positive pregnancy test. Too often results of infertility trials are lacking in crucial obstetric details. This is problematic because treatments for infertility have the capacity to increase the risk for a variety of adverse obstetric outcomes. This review will outline important obstetric variables that should be included when reporting infertility research. The rationale for including these data, precise definitions of the variables, and cost-effective strategies for obtaining these obstetric details will be highlighted. Copyright © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc.


Objective: To examine the early reading skills of young children with cleft lip and palate and to examine the relationship between early reading skills and speech and language performance. Participants: A total of 56 children participated in the study: 28 children with cleft lip and palate and 28 noncleft children matched for age (mean age, 5 years 7 months), gender, and months of formal schooling. Main Outcome Measures: The two groups of children were compared (t tests) on the Test of Early Reading-3. Pearson product moment correlations were performed to examine separately the relationship between early reading skills and speech production abilities and between early reading skills and receptive and expressive language abilities for the two groups. Results: Statistically significant group differences were noted on the Test of Early Reading-3. The mean score of 99 obtained by the group of children with cleft lip and palate was within normal limits compared with the norms for the Test of Early Reading-3; however, 14% of the children with cleft lip and palate scored outside the normal range on the Test of Early Reading-3. Statistically significant correlations were obtained between early reading skills and speech production abilities and between early reading skills and language abilities. Conclusions: Children with cleft lip and palate differed from noncleft peers in speech and early reading skills. Children with the most severe speech problems were the children with the poorest performance on the Test of Early Reading-3. Management of children with cleft lip and palate should include early identification of and intervention for delays in speech, language, and reading. © 2011 The American Cleft Palate-Craniofacial Association.


Carey J.C.,University of Utah
Current Opinion in Pediatrics | Year: 2012

PURPOSE OF REVIEW: At the time of diagnosis of the trisomy 18 and trisomy 13, parents and care providers face difficult and challenging decisions regarding management. Because of the increased infant mortality and developmental outcome associated with both conditions, the conventional approach to management has been to withhold technological support. In recent years, an active dialogue on this topic has emerged. The purpose of this review is to summarize the literature on the outcome of infants with trisomy 18 and 13 and to discuss the key themes in this emerging dialogue. RECENT FINDINGS: In recent years, several important studies have appeared that have analyzed the issues relevant to this topic, including parental autonomy, best interest of the child standard, and quality of life. Some authorities state that in areas of ambiguity it is best to defer to parents' views, whereas others indicate concern that the best interest standard has given way to parental autonomy. Information on the actual experience of parents of children with trisomy 18 and 13 has been limited until recently. SUMMARY: The author recommends a balanced approach to counseling families of the newborn with trisomy 18 and 13 at the time of diagnosis. The counseling process should include presentation of accurate survival figures, avoidance of language that assumes outcome, communication of developmental outcome that does not presuppose perception of quality of life, and respect for the family's choice, whether it be comfort care or intervention. ©2012 Wolters Kluwer Health Lippincott Williams & Wilkins.


Kendall K.A.,University of Utah
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2012

Purpose of review: This review presents recent advances in high-speed digital imaging (HSDI) of the larynx including data acquisition, data analysis, and clinical applicability. Recent findings: Software designed to summarize the large amounts of data captured with HSDI makes it possible to quantitatively analyze recordings from patients, improving the accuracy of the methodology. The new software has been used in studies of normal individuals, increasing our knowledge of normal vocal fold vibratory behavior. HSDI has also been used in patient populations and shows promise in distinguishing various laryngeal conditions that are difficult to distinguish with other imaging modalities. Studies of postoperative patients with HSDI demonstrate the return of some vibratory characteristics but not others, potentially leading the way to improvements in surgical technique. Summary: Recent advances in HSDI technology have increased the clinical usefulness of the imaging technology and recent studies demonstrate the clinical applicability of HSDI. However, challenges to widespread clinical use of HSDI remain. © 2012 Lippincott Williams & Wilkins.


Hurricane Sandy (2012) is known as an incredibly destructive storm and one defined meteorologically by its large size, and its significant forecast track spreads among various operational models roughly 1week before landfall. While the operational European Centre for Medium-Range Weather Forecasts model accurately depicted a northeastern United States landfall, the Global Forecasting System (GFS) model consistently forecast a track toward the North Atlantic Ocean. Using a Weather Research and Forecasting (WRF) model framework, Bassill () suggested that these differences were primarily a function of differences between the two models' cumulus parameterization (CP). This study also uses a WRF model framework to examine the simplified Arakawa Schubert CP used in the GFS model. It is found that increasing the deep convective entrainment coefficient produces more realistic forecast tracks for forecasts initialized roughly 1week before landfall. This occurs through a reorientation of the precipitation (and associated latent heating) around Sandy during a critical time period in which it was interacting with a series of upper troughs to its west and northwest. Reorienting the latent heating reshapes the upper tropospheric steering pattern toward the one that is more negatively tilted and consistent with observations. ©2014. American Geophysical Union. All Rights Reserved.


Jefferies K.,University of Utah
Seminars in Neurology | Year: 2010

Neuropathic pain is a common symptom associated with peripheral neuropathy and can be as or more disabling than the effects of nerve damage from the neuropathy. Though treatment of the underlying pathophysiology causing neuropathies may not be possible, treatment of neuropathic pain is. The author reviews the major medications used, dosing schedules, and data from randomized controlled trials. © 2010 by Thieme Medical Publishers, Inc.


Whitesell J.,University of Utah
Seminars in Neurology | Year: 2010

Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP. © 2010 by Thieme Medical Publishers, Inc.


A new physical model is put forth to allow the prediction of electron transfer rates and distances for (i) intramolecular transfer from an n ≥ 3 Rydberg orbital on a positive site to a disulfide or amide bond site and (ii) intermolecular transfer from an anion donor to an n ≥ 3 Rydberg orbital of a positively charged polypeptide. Although ab initio methods have proven capable of handling such electron transfer events when the Rydberg orbital has principal quantum number n = 3, they have proven to be incapable of handling Rydberg states having quantum number n > 3, so having a new tool capable of handling n > 3 Rydberg states is important. The model (i) focuses on each Rydberg orbitals large peak of high amplitude, (ii) approximates the electron density within this peak as constant within a radial shell characterized by a radius and thickness T both of which depend on the quantum number n, and (iii) assumes that strong coupling (either with an orbital of an anion donor or to a disulfide s* or a backbone amide π* orbital) occurs when the valence orbital penetrates fully within the radial shell of the Rydberg orbital. These assumptions permit a derivation of the ratios of rates of electron transfer for n > 3 to those for n = 3. Combining these ratios with ab initio rates for n = 3 allows one to make rate predictions for inter- and intramolecular electron transfer involving Rydberg orbitals appropriate to the electron transfer dissociation process. One important prediction of this model is that the combination of large-penetration and Landau-Zener surface-crossing conditions places very severe limitations on which Rydberg levels can initially be populated in electron transfer dissociation. Another prediction is that a Rydberg orbital of a given principal quantum number n has a limited range of distances over which it can transfer an electron; s* or π* orbitals either too far from or too close to a given Rydberg orbital cannot accept an electron from that orbital. © 2010 American Chemical Society.


Manaster B.J.,University of Utah
American Journal of Roentgenology | Year: 2013

OBJECTIVE. Soft-tissue masses derive from a wide spectrum of tissues, and it may be difficult to differentiate nonneoplastic from neoplastic as well as benign from malignant lesions, to say nothing of making a single histologic diagnosis on the basis of imaging. The purpose of this article is to discuss optimal imaging protocols and reporting of soft-tissue masses. CONCLUSION. The radiologist should be prepared, if at all possible, to knowledgably examine the patient, optimize an imaging protocol, and differentiate among lesions. Specific features of an MRI examination must be discussed in each report to completely evaluate the mass and perform efficacious biopsy, staging, and eventual treatment of the lesion. Careful and systematic reporting of the examinations should avoid the devastating consequences of either overlooking a sarcoma or overtreating a benign lesion. © American Roentgen Ray Society.


Roy N.,University of Utah
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2011

Purpose of review: The external branch of the superior laryngeal nerve (ESLN) innervates the cricothyroid muscle of the larynx, a vocal fold tensor primarily responsible for pitch elevation. A longstanding controversy is revisited regarding the laryngeal and phonatory signs that should be considered indicative of unilateral ESLN paralysis/paresis. Recent findings: Diagnosis of unilateral ESLN paralysis remains challenging. Despite advances in laryngeal electromyography and improved techniques to visualize the larynx, there is no consensus regarding whether any laryngoscopic or phonatory features should be considered pathognomonic. Laryngeal and voice manifestations may reflect the pure effects of unilateral ESLN dysfunction, or, alternatively, compensatory muscular adjustments in response to prolonged denervation. However, recent in-vivo modeling of ESLN paralysis combined with clinical case studies suggests that deviation of the petiole of the epiglottis to the side of cricothyroid muscle weakness (during high-pitch voice production) may represent a potentially valuable diagnostic sign of both acute and chronic unilateral ESLN denervation. Summary: The absence of reliable diagnostic laryngoscopic signs renders it difficult to determine the prevalence, impact, and treatment of unilateral cricothyroid muscle dysfunction. Research is necessary to assess the precision of epiglottic petiole deviation as a possible marker of unilateral ESLN denervation. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Public policy discourse about cyber security in the United States is dominated by a metaphor of war and analogies to the Cold War. This essay critically evaluates the contradictory tendency within U.S. cyber war discourse to see cyber conflict as simultaneously revolutionary and unprecedented, but also amenable to the tenets of Cold War nuclear deterrence. This contradiction points to an ongoing crisis of effectively identifying and understanding what is old and new, the same and different about cyber conflict. The first tendency overemphasizes the new/different aspects of cyber conflict while the second simultaneously overemphasizes the old/same aspects. This essay argues that current contradictory tendencies are unproductive and even potentially dangerous. It argues that the war metaphor and nuclear deterrence analogy are neither natural nor inevitable and that abandoning them would open up new possibilities for thinking more productively about the full spectrum of cyber security challenges, including the as-yet unrealized possibility of cyber war.


Ruiz-Irastorza G.,University of the Basque Country | Crowther M.,McMaster University | Branch W.,University of Utah | Khamashta M.A.,Kings College
The Lancet | Year: 2010

The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency. Other clinical manifestations are cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of features related to antiphospholipid syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus and probably in purely obstetric antiphospholipid syndrome. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin. Hydroxychloroquine is a potential additional treatment for this syndrome. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs. © 2010 Elsevier Ltd.


Burbidge S.K.,University of Utah
Journal of Transport Geography | Year: 2012

Travel behavior researchers have long been interested in various factors influencing how individuals make transportation decisions. Research has shown that foreign born residents and recent immigrants to the US exhibit significantly different travel behavior than native born populations in the same regions. This paper expands on that existing research by examining the travel behavior data of 662 students from Brigham Young University (52.1% of whom have lived outside the United States for more than 60 consecutive days). First the paper identifies if an individual's experience living abroad results in a change in travel behavior upon their return to the United States; second, if the foreign location where the experience was gained influences any behavioral change, and if so which regions of the world produce the greatest influence?; and third, if the duration of an individual's residence abroad affects their travel behavior and transportation perceptions upon returning to the United States. The analysis revealed that individuals who have lived abroad do exhibit a significant change in travel behavior upon returning to the United States, and the continent where the individual lived does significantly affect their change in travel behavior. However it appears that this change in behavior upon their return to the United States may be a regression to the mean, manifested by individuals adopting travel behavior similar to the transportation culture of their domestic environment. The location and duration of foreign experience does not have a significant impact on the current travel behavior of the individuals represented in this sample. © 2012 Elsevier Ltd.


Ward J.H.,University of Utah
Current opinion in obstetrics & gynecology | Year: 2010

PURPOSE OF REVIEW: To describe the current status regarding the duration of adjuvant tamoxifen and/or aromatase inhibitors in women with early-stage hormone receptor positive breast cancer. RECENT FINDINGS: Women with early-stage breast cancers that express estrogen and/or progesterone receptors benefit from adjuvant hormonal therapy with antiestrogen drugs. Five years of tamoxifen is the standard to which other approaches have been compared. In premenopausal women, a total of 5 years of adjuvant hormonal therapy using tamoxifen is the preferred approach. In postmenopausal women, aromatase inhibitors alone or in sequence after tamoxifen for 5 years has become the standard of care. The use of antiestrogen therapy for longer than 5 years has been studied in several trials. There is a suggestion that there may be improved disease-free survival in some subgroups, but the clinical significance and magnitude of this benefit remains an open question. Some particularly high-risk subgroups may be candidates for extended adjuvant therapy. In addition to the efficacy of adjuvant hormonal therapy, careful attention must be paid to compliance with the prescribed medication, management of side effects, and evaluation of costs. SUMMARY: There are many approaches to the adjuvant hormonal therapy of breast cancer supported by large trials. No one approach is uniquely superior to others. Longer follow-up may lead to more specific recommendations. Adjuvant hormonal therapy for women with hormone receptor positive breast cancer plays a critical role in the management of early stage hormone receptor positive breast cancer.


Cook T.R.,State University of New York at Buffalo | Stang P.J.,University of Utah
Chemical Reviews | Year: 2015

Researchers discuss the latest developments in the preparation and chemistry of metallacycles and metallacages via coordination. Researchers emphasize on results that have been reported over a period of time. The discussion is organized in a way that highlights both the interdisciplinary nature of the field as well as its maturation from studies that defined structural and synthetic methodologies, to more recent efforts to expand structural complexity and explore functional systems for a suite of applications. A number of excellent reviews also provide further insight into specific areas of the chemistry of metallacycles and cages. Some of these reviews focus on a class of building blocks, including acceptors or donors.


The presence of lupus anticoagulant, moderate-to-high levels of IgG and/or IgM antibodies to beta-2 glycoprotein I or cardiolipin in association with at least one of the two major clinical manifestations (thrombosis and/or pregnancy-related morbidity) are required for a diagnosis of definite antiphospholipid syndrome (APS). The realization that certain negatively charged phospholipid (PL) autoantibodies broadly react with antibodies directed against cardiolipin and may be more reliable and specific markers for APS has led to the search for diagnostic assays with greater predictability for disease evaluation and management. This review focuses on the state-of-the-art analytical and clinical performance of IgG and IgM antibodies directed against negatively charged PLs, specifically phosphatidic acid (aPA), phosphatidylinositol (aPI), and phosphatidylserine (aPS), as well as the APhL assay, which contains a proprietary mixture of phospholipid antigens. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.


Strong C.,University of Utah | Rigor I.G.,University of Washington
Geophysical Research Letters | Year: 2013

Declines in Arctic sea ice extent and thickness suggest scientifically important changes in the spatial pattern of the marginal ice zone (MIZ) - a dynamic and biologically active band of sea ice cover close to open ocean. Arctic MIZ widths were measured in satellite era sea ice concentrations over the years 1979-2011 using a recently published MIZ width analysis method. Over the record, the warm season (July-September) MIZ width increased by 13 km decade-1, amounting to a 39% widening. This widening trend resulted from a marked poleward advancement of the MIZ poleward edge into regions where sea ice was increasingly younger and thinner at the beginning of annual melt, while the MIZ's equatorward edge moved comparatively little. The warm season MIZ widening contrasted in sign and strength with a cold season (February-April) MIZ narrowing trend (4 km decade-1, amounting to a 15% narrowing). © 2013. American Geophysical Union. All Rights Reserved.


White H.S.,University of Utah | Loscher W.,University of Veterinary Medicine Hannover | Loscher W.,Center for Systems Neuroscience
Neurotherapeutics | Year: 2014

A major unmet medical need is the lack of treatments to prevent (or modify) epilepsy in patients at risk, for example, after epileptogenic brain insults such as traumatic brain injury, stroke, or prolonged acute symptomatic seizures like complex febrile seizures or status epilepticus. Typically, following such brain insults there is a seizure-free interval ("latent period"), lasting months to years before the onset of spontaneous recurrent epileptic seizures. The latent period after a brain insult offers a window of opportunity in which an appropriate treatment may prevent or modify the epileptogenic process induced by a brain insult. A similar latent period occurs in patients with epileptogenic gene mutations. Studies using animal models of epilepsy have led to a greater understanding of the factors underlying epileptogenesis and have provided significant insight into potential targets by which the development of epilepsy may be prevented or modified. This review focuses largely on some of the most common animal models of epileptogenesis and their potential utility for evaluating proposed antiepileptogenic therapies and identifying useful biomarkers. The authors also describe some of the limitations of using animal models in the search for therapies that move beyond the symptomatic treatment of epilepsy. Promising results of previous studies designed to evaluate antiepileptogenesis and the role of monotherapy versus polytherapy approaches are also discussed. Recent data from both models of genetic and acquired epilepsies strongly indicate that it is possible to prevent or modify epileptogenesis, and, hopefully, such promising results can ultimately be translated into the clinic. © 2014 The American Society for Experimental NeuroTherapeutics, Inc.


Ampofo K.,University of Utah
Current Opinion in Pediatrics | Year: 2013

PURPOSE OF REVIEW: To provide an update and overview of infectious disease issues in children of international adoption. RECENT FINDINGS: International adoption by US families has decreased since 2004. Countries from where children are adopted have changed by 2011, with Ethiopia the second largest contributor of international adoptees after China. Since 2003, international adoptees are older, as fewer young children (<1 year of age) have been available for adoption. Although children are declared healthy in their home countries, medical disorders are often missed or become apparent after adoption. Comprehensive evaluations by providers in the USA after adoption frequently identify unsuspected medical disorders, infections, as well as delayed or incomplete vaccination in these recently adopted children. Early identification of infections allows treatment of potential communicable diseases and updating of immunizations. SUMMARY: All international adoptees on arrival in the USA should be evaluated by a health practitioner knowledgeable in adoption medicine to identify medical problems, especially infections. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.


Bromberg M.B.,University of Utah
Physical Medicine and Rehabilitation Clinics of North America | Year: 2013

Electrodiagnosis, which includes nerve conduction and needle electromyographic studies, is an essential element in the evaluation of peripheral neuropathies. A systematic approach to the electrodiagnostic evaluation aids in clarifying the distribution and extent of involvement, type of nerve damage, and time course. When these data are combined with clinical information, a full characterization of the neuropathy is possible leading to a sound differential diagnosis and selection of rational tests to order. This article will discuss the relevant anatomy and physiology of peripheral nerves and the principles of nerve conduction and needle electromyographic studies, including how they help distinguish between prototypic examples of primary axonal and demyelinating neuropathies, how to plan electrodiagnostic studies, and how to interpret data from outside studies. © 2013.


Transport through ionic conducting membranes is examined. An equation describing the chemical potential, μs, of electrically neutral species, s, in the membrane is derived in terms of ionic and electronic currents, and ionic and electronic transport resistances. It is shown that the μs in the membrane need not be mathematically bounded by the values at the two electrodes (reservoirs) if the ionic and the electronic currents through the membrane are in the same direction. Conditions could develop under which the μs in the membrane may exceed the thermodynamic stability of the membrane even when exposed to stable conditions at the two electrodes. It is shown that during charging, chemical potential of lithium, μLi, in the electrolyte of a lithium-ion battery may exceed that corresponding to pure lithium thus causing lithium precipitation and/or reaction with the electrolyte. It is also shown that in a lithium ion battery pack containing several cells, degradation may occur during discharge due to cell imbalance. In unbalanced cells, the SEI layer may form at both the anode/electrolyte and the cathode/electrolyte interfaces. A bi-layer separator comprising an electronic conductor and an electronic insulator is proposed for improved stability of lithium batteries. © 2011 Elsevier B.V. All rights reserved.


Mishchenko E.G.,University of Utah
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

A metal film supports the continuum of propagating surface plasmon waves. The interaction of these waves with a dipole (nanoparticle) positioned some distance from the surface of the film can produce well-defined localized plasmon modes whose frequency nonetheless resides inside the continuum. This leads to the resonant enhancement of scattering of surface plasmons off the dipole. The maximum of scattering is found to occur when the distance from the dipole to the surface of the film is equal to one-half of the film thickness. The possibility of controllable plasmon scattering could be advantageous for the field of nanoplasmonics. © 2013 American Physical Society.


Cen R.,Princeton University | Zheng Z.,University of Utah
Astrophysical Journal | Year: 2013

We present a new model for the observed Lyα blobs (LABs) within the context of the standard cold dark matter model. In this model, LABs are the most massive halos with the strongest clustering (protoclusters) undergoing extreme starbursts in the high-z universe. Aided by calculations of detailed radiative transfer of Lyα photons through ultrahigh resolution (159 pc), large-scale (≥30 Mpc) adaptive mesh refinement cosmological hydrodynamic simulations with galaxy formation, this model is shown to be able to, for the first time, reproduce simultaneously the global Lyα luminosity function and the luminosity-size relation of the observed LABs. Physically, a combination of dust attenuation of Lyα photons within galaxies, clustering of galaxies, and the complex propagation of Lyα photons through the circumgalactic and intergalactic medium gives rise to the large sizes and the irregular isophotal shapes of LABs that are frequently observed. A generic and unique prediction of this model is that there should be strong far-infrared (FIR) sources within each LAB with the most luminous FIR source likely representing the gravitational center of the protocluster, not necessarily the apparent center of the Lyα emission of the LAB or the most luminous optical source. Upcoming ALMA observations should unambiguously test this prediction. If verified, LABs will provide very valuable laboratories for studying the formation of galaxies in the most overdense regions of the universe at a time when the global star formation was the most vigorous. © 2013. The American Astronomical Society. All rights reserved..


Cereda A.,University of Milan Bicocca | Carey J.C.,University of Utah
Orphanet Journal of Rare Diseases | Year: 2012

The trisomy 18 syndrome, also known as Edwards syndrome, is a common chromosomal disorder due to the presence of an extra chromosome 18, either full, mosaic trisomy, or partial trisomy 18q. The condition is the second most common autosomal trisomy syndrome after trisomy 21. The live born prevalence is estimated as 1/6,000-1/8,000, but the overall prevalence is higher (1/2500-1/2600) due to the high frequency of fetal loss and pregnancy termination after prenatal diagnosis. The prevalence of trisomy 18 rises with the increasing maternal age. The recurrence risk for a family with a child with full trisomy 18 is about 1%. Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities (e.g., increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects). The recognizable syndrome pattern consists of major and minor anomalies, prenatal and postnatal growth deficiency, an increased risk of neonatal and infant mortality, and marked psychomotor and cognitive disability. Typical minor anomalies include characteristic craniofacial features, clenched fist with overriding fingers, small fingernails, underdeveloped thumbs, and short sternum. The presence of major malformations is common, and the most frequent are heart and kidney anomalies. Feeding problems occur consistently and may require enteral nutrition. Despite the well known infant mortality, approximately 50% of babies with trisomy 18 live longer than 1 week and about 5-10% of children beyond the first year. The major causes of death include central apnea, cardiac failure due to cardiac malformations, respiratory insufficiency due to hypoventilation, aspiration, or upper airway obstruction and, likely, the combination of these and other factors (including decisions regarding aggressive care). Upper airway obstruction is likely more common than previously realized and should be investigated when full care is opted by the family and medical team. The complexity and the severity of the clinical presentation at birth and the high neonatal and infant mortality make the perinatal and neonatal management of babies with trisomy 18 particularly challenging, controversial, and unique among multiple congenital anomaly syndromes. Health supervision should be diligent, especially in the first 12 months of life, and can require multiple pediatric and specialist evaluations. © 2012 Cereda and Carey; licensee BioMed Central Ltd.


Cook A.E.,University of Utah
Memory and Cognition | Year: 2014

Previous researchers have demonstrated that readers may engage in shallow, or incomplete, processing when the semantic overlap between current information and previously encountered information is high. The present study investigated whether these effects would occur during processing of unambiguous noun phrase anaphors, for which there was only a single possible antecedent. Participants read passages containing anaphors that were correct, incorrect but highly related, or incorrect and low-related, with respect to previously encountered information. The time required to process the anaphor was a function of the goodness of fit between the anaphor and the antecedent; anaphors that were incorrect but highly related to the antecedent were processed more quickly than those that were incorrect and low-related. This occurred regardless of the distance between the anaphor and the antecedent. However, reading times results from a spillover sentence indicated that readers subsequently validated the anaphor against the information in memory, resulting in continued processing difficulty for both the incorrect-high- and –low-related anaphor conditions. The results are consistent with a three-stage comprehension model in which information is activated, integrated on the basis of its goodness of fit with the contents of working memory, and then validated against information in long-term memory. © 2014, Psychonomic Society, Inc.


Taha S.A.,University of Utah
Physiology and Behavior | Year: 2010

It is well established that opioid signaling in the central nervous system constitutes a powerful stimulus for food intake. The role of opioids in determining food preference, however, is less well defined. Opioids have been proposed to promote intake of preferred foods, or, alternatively, to preferentially increase consumption of fat. In the present manuscript, I comprehensively review results from previous studies investigating this issue. Data from these studies suggests a mechanism for opioid action that may reconcile the previously proposed hypotheses: opioid effects on food intake do appear to be largely specific for fat consumption, but individual animals' sensitivity to this effect may be dependent on baseline food preferences. In addition, I highlight the possibility that the selectivity of endogenous opioid effects may importantly differ from that of exogenous agonists in the degree to which baseline preferences, rather than macronutrient intake, are altered. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. © 2010 Elsevier Inc.


Rates of cesarean delivery have substantially increased worldwide during the past 30 years. Indeed, almost one-third of deliveries in the United States are cesareans. Most cesareans are safe, and major complications are uncommon. However, there is a "concealed" downside to cesarean deliveries. There are rare but life-threatening morbidities that may occur, which are often overlooked because most cesareans go well. In addition, subsequent pregnancies are fraught with an increased risk of both maternal and fetal complications. The worst of these are associated with placental problems such as previa, abruption, and accreta. The risk dramatically worsens in patients with multiple repeat cesarean deliveries. This article will summarize and highlight the implications of the rising cesarean rate on maternal and fetal morbidity and mortality. © 2012 Elsevier Inc.


Kiefer J.C.,University of Utah
Developmental Dynamics | Year: 2011

A stem cell niche is a microenvironment that supports self-renewal of a population of stem cells, and their production of differentiated cells. While the definition evokes images of a stem cell Shangri-La-where a serene stem cell pool nestles within a niche that shelters and sustains it-the reality is much more tumultuous. Niches are subject to an ever-changing maelstrom of environmental factors, the ravages of old age, and the sly tactics of disease. Presented here is a basic overview of the different ways in which stem cell niches respond to local and systemic environments, and their impact on stem cell behavior. The primer culminates with a discussion of the topic with stem cell and niche biologists D. Leanne Jones, Ph.D., and Tudorita Tumbar, Ph.D. Developmental Dynamics 240:737-743, 2011. © 2011 Wiley-Liss, Inc.


Hollien J.,University of Utah
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

The unfolded protein response (UPR) is a network of signaling pathways that responds to stress in the endoplasmic reticulum (ER). The general output of the UPR is to upregulate genes involved in ER function, thus restoring and/or increasing the capacity of the ER to fold and process proteins. In parallel, many organisms have mechanisms for limiting the load on the ER by attenuating translation or degrading ER-targeted mRNAs. Despite broad conservation of these signaling pathways across eukaryotes, interesting variations demonstrate a variety of mechanisms for managing ER stress. How do early-diverging protozoa respond to stress when they lack traditional transcriptional regulation? What is the role of the ER stress sensor Ire1 in fungal species that are missing its main target? Here I describe how diverse species have optimized the UPR to fit their needs. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum. © 2013 Elsevier B.V.


Carroll D.,University of Utah
Genetics | Year: 2011

Zinc-finger nucleases (ZFNs) are targetable DNA cleavage reagents that have been adopted as gene-targeting tools. ZFNinduced double-strand breaks are subject to cellular DNA repair processes that lead to both targeted mutagenesis and targeted gene replacement at remarkably high frequencies. This article briefly reviews the history of ZFN development and summarizes applications that have been made to genome editing in many different organisms and situations. Considerable progress has been made in methods for deriving zinc-finger sets for new genomic targets, but approaches to design and selection are still being perfected. An issue that needs more attention is the extent to which available mechanisms of double-strand break repair limit the scope and utility of ZFNinitiated events. The bright prospects for future applications of ZFNs, including human gene therapy, are discussed. © 2011 by the Genetics Society of America.


Amann M.,University of Utah
Medicine and Science in Sports and Exercise | Year: 2011

Existing evidence suggests that exercise-induced alterations of the metabolic milieu of locomotor muscle and associated peripheral muscle fatigue affect the central projection of thin-fiber muscle afferents. These neurons provide inhibitory feedback to the CNS and thereby influence the magnitude of central motor drive during high-intensity whole-body endurance exercise. The purpose of this proposed feedback loop would be to regulate and restrict the development of exercise-induced peripheral muscle fatigue and/or associated sensory feedback to an "individual critical threshold." This centrally mediated restriction in the development of peripheral locomotor muscle fatigue might thereby help to prevent excessive disturbance of muscle homeostasis and potential harm to the organism. It seems that the regulatory mechanism is dominant during exercise under "normal" conditions but might become secondary in the face of extreme environmental influences such as severe hypoxia or heat. Most recent data are used to emphasize how the proposed feedback loop might be a key factor limiting performance during high-intensity whole-body endurance exercise. © 2011 by the American College of Sports Medicine.


Sun Y.,University of Utah
American Journal of Public Health | Year: 2014

I reexamine the notion of public health after reviewing critiques of the prevalent individualistic conception of health. I argue that public health should mean not only the health of the public but also health in the public and by the public, and I expound on the social contingency of health and highlight the importance of the interpersonal dimensions of health conditions and health promotion efforts. Promoting public health requires activating health-enhancing communicative behaviors (such as interpersonal advocacy and mutual responsibility taking) in addition to individual behavioral change. To facilitate such communicative behaviors, it is imperative to first construct a new discursive environment in which to think and talk about health in a language of interdependence and collective efforts.


Hoepfner M.P.,University of Utah | Fogler H.S.,University of Michigan
Langmuir | Year: 2013

Small-angle X-ray and neutron scattering (SAXS/SANS) by asphaltenes in various solvents (toluene, tetrahydrofuran, and 1-methylnaphthalene) at dilute concentrations of asphaltenes are presented and discussed. As asphaltenes are diluted, it was found that the cluster size decreases and follows a fractal scaling law. This observation reveals that asphaltene clusters persist to dilute concentrations and maintain fractal characteristics, regardless of concentration. For the first time, the fraction of asphaltenes that exist in nanoaggregates compared to those molecularly dispersed was estimated from the scattering intensity. Significant dissociation was detected at concentrations similar to the previously reported critical nanoaggregate concentration (CNAC); however, the dissociation was observed to occur gradually as the asphaltene concentration was lowered. Complete dissociation was not detected, and aggregates persisted down to asphaltene concentrations as low as 15 mg/L (0.00125 vol. %). A simplified thermodynamic aggregation model was applied to the measurements, and the free energy change of association per asphaltene-asphaltene interaction was calculated to be approximately -31 kJ/mol. Finally, novel solvent-corrected WAXS results of asphaltene in a liquid environment are presented and reveal three distinct separation distances, in contrast to the two separation distances observed in diffraction studies of solid phase asphaltenes. Significant differences in the WAXS peak positions and shapes between aromatic and nonaromatic solvents suggests that there may be large differences between the solvation shell or conformation of the asphaltene alkyl shell depending on the surrounding liquid environment. © 2013 American Chemical Society.


Kohan D.E.,University of Utah | Barton M.,University of Zurich
Kidney International | Year: 2014

The incidence and prevalence of chronic kidney disease (CKD), with diabetes and hypertension accounting for the majority of cases, is on the rise, with up to 160 million individuals worldwide predicted to be affected by 2020. Given that current treatment options, primarily targeted at the renin-angiotensin system, only modestly slow down progression to end-stage renal disease, the urgent need for additional effective therapeutics is evident. Endothelin-1 (ET-1), largely through activation of endothelin A receptors, has been strongly implicated in renal cell injury, proteinuria, inflammation, and fibrosis leading to CKD. Endothelin receptor antagonists (ERAs) have been demonstrated to ameliorate or even reverse renal injury and/or fibrosis in experimental models of CKD, whereas clinical trials indicate a substantial antiproteinuric effect of ERAs in diabetic and nondiabetic CKD patients even on top of maximal renin-angiotensin system blockade. This review summarizes the role of ET in CKD pathogenesis and discusses the potential therapeutic benefit of targeting the ET system in CKD, with attention to the risks and benefits of such an approach. © 2014 International Society of Nephrology.


Hedlund G.L.,University of Utah
Pediatric Radiology | Year: 2013

Cerebral sinovenous thrombosis (CSVT) in the pediatric population is a relatively uncommon yet under-appreciated and potentially life-threatening neurological condition. Early symptoms and signs are often vague and the clinician requesting a cranial imaging study might not even suspect sinovenous thrombosis. If left undiagnosed, or if the diagnosis of CSVT is delayed, progressive neurological deterioration, coma and death can follow. The purpose of this review is to highlight pertinent development of the cerebral venous system, discuss the causal factors of cerebral sinovenous thrombosis in the pediatric population, review practical imaging strategies using cranial sonography augmented with color and pulsed Doppler, unenhanced brain CT, CT venography, cerebral MRI, and MR venography (MRV). Finally, this review will illustrate the imaging features of sinovenous thrombosis, including a discussion of the common causes of false-positive and false-negative CT and MRI studies. © 2012 Springer-Verlag.


Hartnett M.E.,University of Utah
Clinics in Perinatology | Year: 2014

In this article, the growing problem of retinopathy of prematurity (ROP) worldwide, treatments for severe ROP including standard-of-care laser treatment, and the need for new treatments are discussed. Also discussed are the reasons to consider inhibiting the vascular endothelial growth factor (VEGF) signaling pathway in severe ROP and the concerns about broad VEGF inhibition. Finally, the potential role of VEGF in ROP based on studies in animal models of oxygen-induced retinopathy, the effects of anti-VEGF based on basic research data, and the clinical relevance of these data are covered. © 2014 Elsevier Inc.


Adelman M.R.,University of Utah
Journal of Lower Genital Tract Disease | Year: 2014

OBJECTIVE: To describe novel innovations and techniques for the detection of high-grade dysplasia. MATERIALS AND METHODS: Studies were identified through the PubMed database, spanning the last 10 years. The key words (["computerized colposcopy" or "digital colposcopy" or "spectroscopy" or "multispectral digital colposcopy" or "dynamic spectral imaging", or "electrical impedance spectroscopy" or "confocal endomicroscopy" or "confocal microscopy"or "optical coherence tomography"] and ["cervical dysplasia" or cervical precancer" or "cervix" or "cervical"]) were used. The inclusion criteria were published articles of original research referring to noncolposcopic evaluation of the cervix for the detection of cervical dysplasia. Only English-language articles from the past 10 years were included, in which the technologies were used in vivo, and sensitivities and specificities could be calculated. RESULTS: The single author reviewed the articles for inclusion. Primary search of the database yielded 59 articles, and secondary cross-reference yielded 12 articles. Thirty-two articles met the inclusion criteria. CONCLUSIONS: An instrument that globally assesses the cervix, such as computer-assisted colposcopy, optical spectroscopy, and dynamic spectral imaging, would provided the most comprehensive estimate of disease and is therefore best suited when treatment is preferred. Electrical impedance spectroscopy, confocal microscopy, and optical coherence tomography provide information at the cellular level to estimate histology and are therefore best suited when deferment of treatment is preferred. If a device is to eventually replace the colposcope, it will likely combine technologies to best meet the needs of the target population, and as such, no single instrument may prove to be universally appropriate. Analyses of false-positive rates, additional colposcopies and biopsies, cost, and absolute life-savings will be important when considering these technologies and are limited thus far. © 2014, American Society for Colposcopy and Cervical Pathology.


De Schweinitz P.,University of Utah
Annals of Family Medicine | Year: 2015

Behavioral change is at the heart of effective primary care, but when patients don’t change, how do we account for our days? In this personal essay, I relate an encounter with a patient who wants to quit smoking, lose weight, and control her diabetes. I am discouraged when she deflects my recommendations, but a colleague’s comment encourages a deeper inquiry. Knowing the patient’s story and deepening the conversation, however, do not guarantee change. The experience reminds me why patience, humility, and faith are core values of the primary care physician. © Annals of Family Medicine, Inc. All rights reserved.


Lin J.,California Polytechnic State University, San Luis Obispo | Keener J.P.,University of Utah
Biophysical Journal | Year: 2014

The effect of gap junctional coupling, sodium ion channel distribution, and extracellular conductivity on transverse conduction in cardiac tissue is explored using a microdomain model that incorporates aspects of the inhomogeneous cellular structure. The propagation velocities found in our model are compared to those in the classic bidomain model and indicate a strong ephaptic microdomain contribution to conduction depending on the parameter regime. We show that ephaptic effects can be quite significant in the junctional spaces between cells, and that the cell activation sequence is modified substantially by these effects. Further, we find that transverse propagation can be maintained by ephaptic effects, even in the absence of gap junctional coupling. The mechanism by which this occurs is found to be cablelike in that the junctional regions act like inverted cables. Our results provide insight into several recent experimental studies that indirectly indicate a mode of action potential propagation that does not rely exclusively on gap junctions. © 2014 Biophysical Society.


Garrison A.,University of Utah
American Family Physician | Year: 2015

Gestational diabetes mellitus (GDM) affects approximately 6% of pregnancies in the United States, and it is increasing in prevalence. Pregnant women without known diabetes mellitus should be screened for GDM after 24 weeks of gestation. Treatment of GDM results in a statistically significant decrease in the incidence of preeclampsia, shoulder dystocia, and macrosomia. Initial management includes glucose monitoring and lifestyle modifications. If glucose levels remain above target values, pharmacologic therapy with metformin, glyburide, or insulin should begin. Antenatal testing is customary for women requiring medications. Induction of labor should not occur before 39 weeks in women with GDM, unless glycemic control is poor or another indication for delivery is present. Unless otherwise indicated, scheduled cesarean delivery should be considered only in women with an estimated fetal weight greater than 4,500 g. Women with a history of GDM are at high risk of subsequently developing diabetes. These patients should be screened six to 12 weeks postpartum for persistently abnormal glucose metabolism, and should undergo screening for diabetes every three years thereafter. © 2015, American Academy of Family Physicians. All rights reserved.


Hopkins P.N.,University of Utah
Physiological Reviews | Year: 2013

At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-α and related family members leading to activation of NF-κB; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world. © 2013 the American Physiological Society.


A heretofore-unavailable mixed Frobenius type series, in terms of affine-transformed x-y coordinate variables of the Eshelby-Stroh type, is introduced to develop a new eigenfunction expansion technique. This is used, in conjunction with separation of the z-variable, to derive three-dimensional mixed-mode I+II+III asymptotic displacement and stress fields in the vicinity of the front of a semi-infinite through-thickness (111) [1̄1̄2 ] × [11̄0] crack weakening an infinite diamond cubic mono-crystalline plate. Crack-face boundary conditions and those that are prescribed on the top and bottom (free, fixed or lubricated) surfaces of the diamond cubic mono-crystalline plate are exactly satisfied. Explicit expressions for the mixed mode I+II+III singular stresses in the vicinity of the front of the through-thickness crack, are presented. Most important mixed modes I+II+III response is elicited even though the far-field loading is only mode I or II or III or any combination thereof. Finally, atomistic modeling of cracks requires consideration of both the long range elastic interactions and the short range physico-chemical reactions, such as bond breaking. The Griffith-Irwin approach does not take the latter into account, and nano-structural details such as bond orientation must be accounted for. A new mixed-mode I+II+III crack deflection criterion elucidates the formation of steps and/or triangular ridges on the crack path. The planes of a multiply deflected crack are normal to the directions of broken bonds. Additionally, the mixed-mode (I+II+III) crack deflection and ridge formation are found to be strongly correlated with the elastic stiffness constants, c14 and c56, of the diamond cubic single crystal concerned. © 2014 Springer Science+Business Media Dordrecht.


Kious B.M.,University of Utah
Philosophy, Psychiatry and Psychology | Year: 2015

Autonomy is the property of individuals’ decisions that makes them immune to paternalistic interference. Conventionally, a decision is taken to be autonomous if and only if it is competent (rational and well informed) and voluntary (made by the agent herself). This theory of autonomy is ostensibly value-neutral, because competence and voluntariness are thought to be independent of the merits of the decision-maker’s values. I argue, however, that the non-autonomy of several classes of decisions (made by persons with anorexia nervosa, drug addiction, and depression, and by children) can be explained neither by incompetence nor by a value-neutral conception of voluntariness. Instead, if these decisions really are non-autonomous, it is because voluntariness, and so autonomy, can be undermined when a person’s values do not reflect accurately her own objective good. In such cases, autonomy is not as value-neutral as it may seem, and attempts to explicate the non-autonomy of these decisions in a value-neutral fashion seem to succeed largely insofar as their criteria are indirect evidence of inappropriate values. © 2015 by The Johns Hopkins University Press


Kesner R.P.,University of Utah | Rolls E.T.,Oxford Center for Computational Neuroscience | Rolls E.T.,University of Warwick
Neuroscience and Biobehavioral Reviews | Year: 2015

The aims of the paper are to update Rolls' quantitative computational theory of hippocampal function and the predictions it makes about the different subregions (dentate gyrus, CA3 and CA1), and to examine behavioral and electrophysiological data that address the functions of the hippocampus and particularly its subregions. Based on the computational proposal that the dentate gyrus produces sparse representations by competitive learning and via the mossy fiber pathway forces new representations on the CA3 during learning (encoding), it has been shown behaviorally that the dentate gyrus supports spatial pattern separation during learning. Based on the computational proposal that CA3-CA3 autoassociative networks are important for episodic memory, it has been shown behaviorally that the CA3 supports spatial rapid one-trial learning, learning of arbitrary associations where space is a component, pattern completion, spatial short-term memory, and spatial sequence learning by associations formed between successive items. The concept that the CA1 recodes information from CA3 and sets up associatively learned backprojections to neocortex to allow subsequent retrieval of information to neocortex, is consistent with findings on consolidation. Behaviorally, the CA1 is implicated in processing temporal information as shown by investigations requiring temporal order pattern separation and associations across time; and computationally this could involve associations in CA1 between object and timing information that have their origins in the lateral and medial entorhinal cortex respectively. The perforant path input from the entorhinal cortex to DG is implicated in learning, to CA3 in retrieval from CA3, and to CA1 in retrieval after longer time intervals ("intermediate-term memory") and in the temporal sequence memory for objects. © 2014 Elsevier Ltd.


Amann M.,University of Utah
Clinical and Experimental Pharmacology and Physiology | Year: 2012

With the onset of dynamic whole-body exercise, contraction-induced mechanical and biochemical stimuli within locomotor muscle cause an increase in the discharge frequency of thinly myelinated (Group III) and unmyelinated (Group IV) nerve fibres located within the muscle. These thin fibre muscle afferents project to various sites within the central nervous system and thereby substantially influence the exercising human. First, Group III/IV muscle afferents are the afferent arm of cardiovascular and ventilatory reflex responses that are mediated in the nucleus tractus solitarius and the ventrolateral medulla. Therefore, neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O2 delivery determine the fatigability of skeletal muscle. Second, Group III/IV muscle afferents facilitate 'central fatigue' (failure, or unwillingness, of the central nervous system to 'drive' motoneurons) by exerting inhibitory influences on central motor drive during exercise. Thus, Group III/IV muscle afferents play a substantial role in a human's susceptibility to fatigue and capacity for endurance exercise. Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.


Riede T.,University of Utah
Journal of Experimental Zoology Part A: Ecological Genetics and Physiology | Year: 2013

Rodents produce highly variable ultrasound whistles as communication signals unlike many other mammals, who employ flow-induced vocal fold oscillations to produce sound. The role of larynx muscles in controlling sound features across different call types in ultrasound vocalization (USV) was investigated using laryngeal muscle electromyographic (EMG) activity, subglottal pressure measurements and vocal sound output in awake and spontaneously behaving Sprague-Dawley rats. Results support the hypothesis that glottal shape determines fundamental frequency. EMG activities of thyroarytenoid and cricothyroid muscles were aligned with call duration. EMG intensity increased with fundamental frequency. Phasic activities of both muscles were aligned with fast changing fundamental frequency contours, for example in trills. Activities of the sternothyroid and sternohyoid muscles, two muscles involved in vocal production in other mammals, are not critical for the production of rat USV. To test how stereotypic laryngeal and respiratory activity are across call types and individuals, sets of ten EMG and subglottal pressure parameters were measured in six different call types from six rats. Using discriminant function analysis, on average 80% of parameter sets were correctly assigned to their respective call type. This was significantly higher than the chance level. Since fundamental frequency features of USV are tightly associated with stereotypic activity of intrinsic laryngeal muscles and muscles contributing to build-up of subglottal pressure, USV provide insight into the neurophysiological control of peripheral vocal motor patterns. © 2013 Wiley Periodicals, Inc.


Lupton J.M.,University of Regensburg | Lupton J.M.,University of Utah
ChemPhysChem | Year: 2012

What is the physical shape of the π-electron system in a large macromolecule such as a conjugated polymer? Although intuitively one may argue that any departure from rigidity by bending or twisting should disrupt conjugation, leading to the formation of discrete chromophores, single-molecule and ensemble time-resolved studies support the notion that the π-bond is remarkably persistent in space: even individual chromophores can be bent and twisted, so that caution is warranted when interpreting a wide range of polarisation-based spectroscopies. What shape is it? Single-molecule and ensemble time-resolved studies support the notion that the π-bond in large macromolecules, such as conjugated polymers, is remarkably persistent in space: even individual chromophores can be bent and twisted, so that caution is warranted when interpreting a wide range of polarization-based spectroscopies. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Digre K.B.,University of Utah
Journal of Neuro-Ophthalmology | Year: 2011

Management of the pregnant woman with a neuro-ophthalmic disorder may be challenging. Physiologic changes in pregnancy make vascular conditions more frequent, including retinal artery occlusion, spontaneous orbital hemorrhage, and pituitary apoplexy. Papilledema may signal cerebral venous sinus thrombosis or idiopathic intracranial hypertension. Manifestations of severe preeclampsia and eclampsia include choroidal infarction, serous retinal detachment, and disorders of higher cortical function, such as alexia, simultanagnosia, and cerebral blindness. Cranial neuropathies have also been reported. Transient Horner syndrome, intracranial hypotension with comitant esotropia may occur in the postpartum period. Treatment of the neuro-ophthalmic complications of pregnancy requires an understanding of the risks of medications. Taking optimal care of the mother will usually result in the best care for her baby. © 2011 Lippincott Williams & Wilkins, Inc.


Snow B.W.,University of Utah
Current Opinion in Urology | Year: 2011

Purpose of Review: The undesirable nature of bladder imaging in children for vesicoureteral reflux detection makes the search for noninvasive bladder imaging methods and devices an urgent concern. Recent Findings: Ultrasound imaging of the bladder aided by contrast agents can be performed without ionizing radiation. However, urethral catheterization and contrast instillation is still necessary. The accuracy and reliability are still significant problems with this method. A new method of 'hiding' gadolinium in lysosomes followed by external energy application to rupture the lysosomes releasing the gadolinium for MRI holds future hope, but this research is in its infancy. A novel method to apply external microwave energy to warm the bladder urine with microwave kidney temperature monitoring is being developed. Temperature changes noted in the kidney after bladder warming would indicate vesicoureteral reflux. Further studies are ongoing. Summary: Ultrasonography imaging of the bladder to find vesicoureteral reflux has yet to be refined enough to be accurate and reliable for clinical use. MRI studies are in their infancy but may hold future benefit. Noninvasive bladder heating and kidney temperature monitoring is showing promise in animal studies to be a completely noninvasive reflux detection device. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Starykh O.A.,University of Utah
Reports on Progress in Physics | Year: 2015

We review ground states and excitations of a quantum antiferromagnet on triangular and other frustrated lattices. We pay special attention to the combined effects of magnetic field h, spatial anisotropy R and spin magnitude S. The focus of the review is on the novel collinear spin density wave and spin nematic states, which are characterized by fully gapped transverse spin excitations with Sz =1. We discuss extensively the R - h phase diagram of the antiferromagnet, both in the large-S semiclassical limit and the quantum S = 1/2 limit. When possible, we point out connections with experimental findings. © 2015 IOP Publishing Ltd.


Babu P.V.A.,University of Utah | Liu D.,Virginia Polytechnic Institute and State University | Gilbert E.R.,Virginia Polytechnic Institute and State University
Journal of Nutritional Biochemistry | Year: 2013

Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables, and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is encouraging that the beneficial effects of some flavonoids are at physiological concentrations and comparable to clinically-used anti-diabetic drugs; however, clinical research in this field and studies on the anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, hepatocytes, adipocytes and skeletal myofibers. Flavonoids may exert beneficial effects in diabetes by (i) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (ii) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (iii) reducing insulin resistance, inflammation and oxidative stress in muscle and fat and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue. This review highlights recent findings on the anti-diabetic effects of dietary flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins, flavones and isoflavones, with particular emphasis on the studies that investigated the cellular and molecular mechanisms involved in the beneficial effects of the compounds. © 2013 Elsevier Inc.


Stillman D.J.,University of Utah
Trends in Biochemical Sciences | Year: 2013

The chromatin structure at a promoter can define how a gene is regulated. Studies of two yeast genes expressed in the G1 phase of the cell cycle, HO and CLN2, have provided important paradigms for transcriptional regulation. Although the SBF (Swi4/Swi6 box factor) transcription factor activates both genes, the chromatin landscapes that regulate SBF binding are different. Specifically, the CLN2 promoter is constitutively available for SBF binding, whereas HO has a complex two-step promoter in which chromatin changes in one region allow SBF to bind at a downstream location. These studies reveal the role of chromatin in defining the regulatory properties of promoters. © 2013 Elsevier Ltd.


O'Connell R.M.,University of Utah | Rao D.S.,Laboratory Medicine | Rao D.S.,Jonsson Comprehensive Cancer Center | Rao D.S.,University of California at Los Angeles | And 2 more authors.
Annual Review of Immunology | Year: 2012

The mammalian inflammatory response is a rapid and complex physiological reaction to noxious stimuli including microbial pathogens. Although inflammation plays a valuable role in combating infection, its dysregulation often occurs in people and can cause a variety of pathologies, ranging from chronic inflammation, to autoimmunity, to cancer. In recent years, our understanding of both the cellular and molecular networks that regulate inflammation has improved dramatically. Although much of the focus has been on the study of protein regulators of inflammation, recent evidence also points to a critical role for a specific class of noncoding RNAs, called microRNAs (miRNAs), in managing certain features of the inflammatory process. In this review, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of human inflammatory diseases. © 2012 by Annual Reviews. All rights reserved.


Scott J.R.,University of Utah
Obstetrics and Gynecology | Year: 2011

Once a woman is delivered by cesarean, her options in a subsequent pregnancy are either a planned trial of labor or a planned elective repeat cesarean. There are no randomized trials comparing these two choices to definitively guide patients and physicians. The primary cesarean rate is increasing and vaginal birth after cesarean delivery (VBAC) rates are decreasing. Nonmedical factors have had a major effect on these trends. The 2010 Eunice Kennedy Shriver National Institute of Child Health and Human Development Conference on VBAC, after presenting a detailed analysis of benefits compared with risks, recommended that measures should be taken to assure women that VBAC is available to them. This will require an organized and concerted effort on the part of patients, physicians, and hospitals. To meet patient expectations for a safe and successful outcome with a trial of labor after cesarean delivery (TOLAC), specific management plans, checklists, practical coverage arrangements, and simulation drills are necessary. © 2011 by The American College of Obstetricians and Gynecologists.


Xu W.,The Interdisciplinary Center | Zipser E.J.,University of Utah
Geophysical Research Letters | Year: 2012

This study compares vertical structures and properties of deep convection for continental, monsoonal, and oceanic rainfall regimes based on 13-yr TRMM measurements. There is evident regime separation in convective structures and properties of deep convection: continental and oceanic regimes are at two ends of the spectrum, with monsoon regimes intermediate between them. For example, most of the continental rainfall (70-80%) is contributed by storms having 40-dBZ radar echoes reaching above 6-km, strong ice scattering signature, and lightning flashes. This indicates that continental convection is dominated by robust mixed-phase processes such as freezing of raindrops or riming of graupel supported by strong updrafts. In contrast, less monsoon rainfall (∼40%) or very limited oceanic rainfall (∼10%) involves these vigorous microphysical processes in mixed-phase regions. Though monsoons are intermediate in convective intensity, both current and previous studies show that their active periods are closer to oceanic regimes and their break periods are slightly closer to continental regimes. In short, this study offers novel guidance for categorization of convective properties of three regime archetypes and will be important for future regional, climatological, and modeling studies. Copyright 2012 by the American Geophysical Union.


Fogel A.,University of Utah
Child Development Perspectives | Year: 2011

This article offers the concept of embodied self-awareness (ESA) as a contrast to parental embodied mentalizing, which is presumed to be implicit and outside awareness. ESA, which consists of awareness of both sensorimotor and emotional states, is essential for all forms of human development and self-regulation and is learned via mutual embodied attunement in interpersonal relationship. Failure to develop ESA reflects a dissociation from the experience of living in a human body and is symptomatic of attachment problems and a wide variety of physical and psychological disorders that may be remediated through clinical practices that enhance embodied awareness. © 2011 The Author. Child Development Perspectives © 2011 The Society for Research in Child Development.


Fogel A.,University of Utah
Child Development Perspectives | Year: 2011

This article discusses some of the ways in which dynamic systems approaches have been applied to developmental science. Dynamic systems thinking suggests that (a) there is always change within stability at the level of real-time (microscopic) behavior, and (b) microlevel change provides the seeds for developmental (macroscopic) change. It is only possible to study these propositions using microgenetic designs, case-based studies of change using frequent observations across development. Normal parent-infant relationships smooth out otherwise abrupt developmental transitions using a bridging process. The absence of developmental bridging may reflect problematic or even traumatic growth patterns, suggesting that bridging, a feature of a developmental trajectory, may serve as a diagnostic individual differences variable. © 2011 The Author. Child Development Perspectives © 2011 The Society for Research in Child Development.


Kesner R.P.,University of Utah
Behavioural Processes | Year: 2013

In order to understand the neural mechanism associated with specific forms of interference, this manuscript concentrates on the role of the dorsal and ventral dentate gyrus subregions of the hippocampus in rats. The computational modelers have suggested that the dentate gyrus can provide a neural mechanism that can operate to reduce interference between highly processed similar spatial, contextual or odor inputs to generate pattern separation functions. Pattern separation which is defined as a process to remove redundancy from similar inputs so that events can be separated from each other and interference can be reduced, and in addition can produce a more orthogonal, sparse, and categorized set of outputs. It appears that the anatomical organization of the hippocampus may provide the answer for the importance of interference in mnemonic processing of information. Therefore, in the first part of this paper an anatomical description of the inputs and outputs of the hippocampus as well as its intrinsic circuit is provided. This is followed by the presentation of data to support the role of the dorsal DG in supporting spatial pattern separation, dorsal CA1 in supporting temporal pattern separation for spatial locations and visual objects, ventral DG in supporting odor pattern separation, and ventral CA1 in supporting temporal pattern separation for odors. © 2012 Elsevier B.V.


Baron R.,University of Utah | McCammon J.A.,Howard Hughes Medical Institute
Annual Review of Physical Chemistry | Year: 2013

We review recent developments in our understanding of molecular recognition and ligand association, focusing on two major viewpoints: (a) studies that highlight new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to protein-ligand binding. In particular, we highlight the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in pharmacology applications. © 2013 by Annual Reviews. All rights reserved.


Background: Many quadrupedal species stand bipedally on their hindlimbs to fight. This posture may provide a performance advantage by allowing the forelimbs to strike an opponent with the range of motion that is intrinsic to high-speed running, jumping, rapid braking and turning; the range of motion over which peak force and power can be produced. Methodology/Principal Findings: To test the hypothesis that bipedal (i.e., orthograde) posture provides a performance advantage when striking with the forelimbs, I measured the force and energy produced when human subjects struck from "quadrupedal" (i.e., pronograde) and bipedal postures. Downward and upward directed striking energy was measured with a custom designed pendulum transducer. Side and forward strikes were measured with a punching bag instrumented with an accelerometer. When subjects struck downward from a bipedal posture the work was 43.70±12.59% (mean ± S.E.) greater than when they struck from a quadrupedal posture. Similarly, 47.49±17.95% more work was produced when subjects struck upward from a bipedal stance compared to a quadrupedal stance. Importantly, subjects did 229.69±44.19% more work in downward than upward directed strikes. During side and forward strikes the force impulses were 30.12±3.68 and 43.04±9.00% greater from a bipedal posture than a quadrupedal posture, respectively. Conclusions/Significance: These results indicate that bipedal posture does provide a performance advantage for striking with the forelimbs. The mating systems of great apes are characterized by intense male-male competition in which conflict is resolved through force or the threat of force. Great apes often fight from bipedal posture, striking with both the fore- and hindlimbs. These observations, plus the findings of this study, suggest that sexual selection contributed to the evolution of habitual bipedalism in hominins. © 2011 David R. Carrier.


Repeated assessments are a relatively common occurrence in clinical neuropsychology. The current paper will review some of the relevant concepts (e.g., reliability, practice effects, alternate forms) and methods (e.g., reliable change index, standardized based regression) that are used in repeated neuropsychological evaluations. The focus will be on the understanding and application of these concepts and methods in the evaluation of the individual patient through examples. Finally, some future directions for assessing change will be described. © The Author 2012.


Armentrout P.B.,University of Utah
Journal of the American Society for Mass Spectrometry | Year: 2013

The utility of measuring the energetics of ion-molecule reactions is discussed. After distinguishing between the terms of thermodynamics (macroscopic, equilibrium quantities) and energetics (microscopic and kinetically relevant quantities), the potential energy surfaces for ion-molecule reactions are reviewed and their implications discussed. Equations describing the kinetic energy dependence of ion-molecule reactions are introduced and the effects of entropy on reaction rates and branching ratios are discussed. Several case histories allow an exploration of the utility of accurate thermochemical information and probe how accurate such energetic information must be to be predictive. These case studies include decomposition of hydrated metal dications, the reaction of FeO+ with H2, and fragmentation of a small protonated peptide (GG). These illustrate a range of interesting systems for which accurate energetic information has been influential in understanding the observed reactivity. Comparisons with theory demonstrate that experimental information is still required for truly predictive capability. [Figure not available: see fulltext.] © 2012 American Society for Mass Spectrometry.


Pandolfino J.E.,Northwestern University | Gawron A.J.,University of Utah
JAMA - Journal of the American Medical Association | Year: 2015

IMPORTANCE: Achalasia significantly affects patients' quality of life and can be difficult to diagnose and treat. OBJECTIVE: To review the diagnosis and management of achalasia, with a focus on phenotypic classification pertinent to therapeutic outcomes. EVIDENCE REVIEW: Literature review and MEDLINE search of articles from January 2004 to February 2015. A total of 93 articles were included in the final literature review addressing facets of achalasia epidemiology, pathophysiology, diagnosis, treatment, and outcomes. Nine randomized controlled trials focusing on endoscopic or surgical therapy for achalasia were included (734 total patients). FINDINGS: A diagnosis of achalasia should be considered when patients present with dysphagia, chest pain, and refractory reflux symptoms after an endoscopy does not reveal a mechanical obstruction or an inflammatory cause of esophageal symptoms. Manometry should be performed if achalasia is suspected. Randomized controlled trials support treatments focused on disrupting the lower esophageal sphincter with pneumatic dilation (70%-90% effective) or laparoscopic myotomy (88%-95% effective). Patients with achalasia have a variable prognosis after endoscopic or surgical myotomy based on subtypes, with type II (absent peristalsis with abnormal pan-esophageal high-pressure patterns) having a very favorable outcome (96%) and type I (absent peristalsis without abnormal pressure) having an intermediate prognosis (81%) that is inversely associated with the degree of esophageal dilatation. In contrast, type III (absent peristalsis with distal esophageal spastic contractions) is a spastic variant with less favorable outcomes (66%) after treatment of the lower esophageal sphincter. CONCLUSIONS AND RELEVANCE: Achalasia should be considered when dysphagia is present and not explained by an obstruction or inflammatory process. Responses to treatment vary based on which achalasia subtype is present. Copyright 2015 American Medical Association. All rights reserved.


Bugger H.,Albert Ludwigs University of Freiburg | Abel E.D.,University of Utah
Cardiovascular Research | Year: 2010

Diabetes mellitus increases the risk of developing cardiovascular diseases such as coronary artery disease and heart failure. Studies have shown that the heart failure risk is increased in diabetic patients even after adjusting for coronary artery disease and hypertension. Although the cause of this increased heart failure risk is multifactorial, increasing evidence suggests that derangements in cardiac energy metabolism play an important role. In particular, abnormalities in cardiomyocyte mitochondrial energetics appear to contribute substantially to the development of cardiac dysfunction in diabetes. This review will summarize these abnormalities in mitochondrial function and discuss potential underlying mechanisms. © 2010 The Author.


Starykh O.A.,University of Utah | Balents L.,University of California at Santa Barbara
Physical Review B - Condensed Matter and Materials Physics | Year: 2014

We study the excitation spectrum and dynamical response functions for several quasi-one-dimensional spin systems in magnetic fields without dipolar spin order transverse to the field. This includes both nematic phases, which harbor "hidden" breaking of spin-rotation symmetry about the field and have been argued to occur in high fields in certain frustrated chain systems with competing ferromagnetic and antiferromagnetic interactions, and spin density wave states, in which spin-rotation symmetry is truly unbroken. Using bosonization, field theory, and exact results on the integrable sine-Gordon model, we establish the collective mode structure of these states, and show how they can be distinguished experimentally. © 2014 American Physical Society.


Long-term, locally-based biodiversity monitoring programs are essential for understanding and mitigating the effects of global change on tropical biodiversity while providing capacity-building, environmental education, and public outreach. However, these programs are lacking in most tropical countries. Birds are the best-known major group of organism, comprise excellent environmental indicators, are relatively easy to monitor, and are met with enthusiasm and interest by people worldwide. Bird monitoring programs using mist nets and bird banding (ringing) are especially valuable, as these well-established techniques enable the use of capture-mark-recapture (CMR) models to measure population change and other demographic parameters. Equally important for conservation, the ability to capture and release birds makes it possible to provide hands-on ornithological training and educational activities to students, conservationists, villagers, decision-makers, journalists, and other local people. Bird banding programs provide local jobs for research assistants, who often go on to productive careers in conservation, education, research, or ecotourism. Long-term bird banding stations also provide the nuclei, infrastructure, and staff for monitoring, education, and conservation programs focused on other taxa. As successful examples from Costa Rica and Ethiopia show, bird monitoring programs that integrate conservation, ecological research, environmental education, capacity-building, and income generation are cost-effective tools to achieve the goals of community-based biodiversity conservation and poverty reduction in the developing world. Therefore, locally-based and long-term bird monitoring programs should be encouraged, established, and funded throughout the tropics. © 2011 Elsevier Ltd.


Sheldon K.S.,University of Utah | Tewksbury J.J.,Luc Hoffmann Institute
Ecology | Year: 2014

Environmental temperature variation can influence physiology, biogeography, and life history, with large consequences for ecology, evolution, and the impacts of climate change. Based on the seasonality hypothesis, greater annual temperature variation at high latitudes should result in greater thermal tolerance and, consequently, larger elevational ranges in temperate compared to tropical species. Despite the mechanistic nature of this hypothesis, most research has used latitude as a proxy for seasonality, failing to directly examine the impact of temperature variation on physiology and range size. We used phylogenetically matched beetles from locations spanning 608 of latitude to explore links between seasonality, physiology and elevational range. Thermal tolerance increased with seasonality across all beetle groups, but realized seasonality (temperature variation restricted to the months species are active) was a better predictor of thermal tolerance than was annual seasonality. Additionally, beetles with greater thermal tolerance had larger elevational ranges. Our results support a mechanistic framework linking variation in realized temperature to physiology and distributions. © 2014 by the Ecological Society of America.


Esplin M.S.,University of Utah
Clinical Obstetrics and Gynecology | Year: 2014

The phenotype of spontaneous preterm birth (SPTB) refers to the biochemical and physical characteristics present at the time of preterm delivery. These are the result of the processes that cause this complication. The lack of understanding about the etiologies and our inability to prevent SPTB are because of the complex nature and multiple processes responsible for maintenance of pregnancy and the transition to labor. Any of these processes, when activated prematurely, may lead to SPTB. This article provides an overview of the SPTB phenotype, which may assist with future attempts to reduce in the incidence of SPTB. © 2014, Lippincott Williams & Wilkins.


Economo M.N.,Boston University | White J.A.,University of Utah
PLoS Computational Biology | Year: 2012

Computational studies as well as in vivo and in vitro results have shown that many cortical neurons fire in a highly irregular manner and at low average firing rates. These patterns seem to persist even when highly rhythmic signals are recorded by local field potential electrodes or other methods that quantify the summed behavior of a local population. Models of the 30-80 Hz gamma rhythm in which network oscillations arise through 'stochastic synchrony' capture the variability observed in the spike output of single cells while preserving network-level organization. We extend upon these results by constructing model networks constrained by experimental measurements and using them to probe the effect of biophysical parameters on network-level activity. We find in simulations that gamma-frequency oscillations are enabled by a high level of incoherent synaptic conductance input, similar to the barrage of noisy synaptic input that cortical neurons have been shown to receive in vivo. This incoherent synaptic input increases the emergent network frequency by shortening the time scale of the membrane in excitatory neurons and by reducing the temporal separation between excitation and inhibition due to decreased spike latency in inhibitory neurons. These mechanisms are demonstrated in simulations and in vitro current-clamp and dynamic-clamp experiments. Simulation results further indicate that the membrane potential noise amplitude has a large impact on network frequency and that the balance between excitatory and inhibitory currents controls network stability and sensitivity to external inputs. © 2012 Economo, White.


Burt R.W.,University of Utah
Cancer Prevention Research | Year: 2012

Since the recognition of Lynch syndrome, which confers a high risk of colorectal, uterine, and other cancers, approaches to its diagnosis have included a family history of associated cancers and web-based algorithms. Identification of causative genes now allows a precise diagnosis, thus focusing present efforts on who should have genetic testing. Testing for cancer tissue changes can determine who should have germline genetic testing. Indeed, such tumor testing is now generally recommended for all newly diagnosed colorectal cancer cases. As reported in this issue of the journal by Yurgelun and colleagues (beginning on page 574), large colorectal adenomatous polyps (≥10 mm) from patients with Lynch syndrome exhibit findings similar to those in Lynch syndrome colorectal cancer tissues. This finding indicates that testing larger adenomas in persons at a significant risk for Lynch syndrome can now determine the need for germline genetic testing. Although further study is needed for general application, the present study justifies large polyp testing in high-risk families when cancer tissue is unavailable, albeit negative polyp tissue would not rule out Lynch syndrome, as would negative cancer tissue. ©2012 AACR.


Lee V.S.,University of Utah
Journal of Magnetic Resonance Imaging | Year: 2013

In this 2012 ISMRM Lauterbur Lecture, my goal is to challenge the members of the ISMRM to think critically about how we approach our research. From the perspective of a leader of an academic health sciences center, which is also a health care delivery system, I address three specific questions: Are we developing great technologies? Are we advancing scientific knowledge? Are we advancing human health? Specifically, with respect to increasing pressure in health care to improve patient outcomes and lower costs, I ask members to consider how we select the areas of research we focus on and whether we have sufficiently prioritized research that assesses the impact of our MR methods on patient outcomes. For imaging research to meet higher standards of evidence-based medicine, multicenter consortia should be developed, potentially under the auspices of the ISMRM, and priority should be given to developing investigators with expertise in health services research. © 2013 Wiley Periodicals, Inc.


Jones K.B.,University of Utah
Journal of Pediatric Orthopaedics | Year: 2011

BACKGROUND: Multiple hereditary exostoses, also termed as multiple osteochondromas, is a heritable disorder of connective tissue with primarily orthopaedic clinical manifestations. Understanding of its biological underpinnings has been advanced on a variety of fronts in recent years. METHODS: The multifaceted literature regarding osteochondromagenesis and the major clinical challenges in patients with multiple osteochondromas were reviewed. RESULTS: Consideration of recent advances in molecular biology, biochemistry, and animal modeling of osteochondroma pathogenesis yields a unified model. CONCLUSIONS: Mechanistic details and therapeutic targets have yet to be elucidated, but the general biology of osteochondroma formation is increasingly clear, as well as its implications in the orthopaedic clinical setting. © 2011 Lippincott Williams & Wilkins, Inc.


Miller J.S.,University of Utah
Chemical Society Reviews | Year: 2011

Magnets composed of molecular components that provide both electron spins and spin-coupling pathways can stabilize bulk magnetic ordering. This was first reported for the ionic, zero-dimensional (0-D) electron transfer salt [Fe(C 5Me5)2]+[TCNE]- (TCNE = tetracyanoethylene), which orders as a ferromagnet at Tc = 4.8 K. Later V[TCNE]x (x ∼ 2) was characterized to order above room temperature at 400 K (127 °C). Subsequently, numerous examples of organic- and molecule-based magnets have been characterized. In this critical review, after a discussion of the important aspects of magnetism pertaining to molecule-based magnets, including the determination of the magnetic ordering temperature (Tc) these magnetically ordered materials are reviewed from a perspective of the structural dimensionality (208 references). © The Royal Society of Chemistry 2011.


Rollins M.D.,University of Utah
Current Opinion in Pediatrics | Year: 2012

Purpose of Review: Congenital diaphragmatic hernia (CDH) is a rare developmental defect resulting in variable degrees of lung and pulmonary vasculature hypoplasia. Whereas many high-volume centers have recently reported increased survival rates, this has not been the collective trend. One potential explanation for this is inconsistent perinatal care among centers. Recent Findings: Significant efforts have been made to identify prenatally those fetuses that will be most severely affected. A number of radiologic features have shown promise for achieving this goal as well as identifying fetuses that may benefit from prenatal intervention. When CDH is antenatally diagnosed, early referral to a tertiary center is recommended. Centers that routinely use postnatal management protocols have demonstrated improved overall survival rates including increased survival in high-risk CDH patients. Summary: As a result of advancements in perinatal care, more severely affected newborns with CDH are now surviving. These patients may experience a number of associated morbidities which affect not only their health but overall quality of life. A multidisciplinary approach to the long-term care of these patients will allow early identification and management of these morbidities. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Jorgenson A.K.,University of Utah
Nature Climate Change | Year: 2014

Humans use fossil fuels in various activities tied to economic development, leading to increases in carbon emissions, and economic development is widely recognized as a pathway to improving human well-being. Strategies for effective sustainability efforts require reducing the carbon intensity of human well-being (CIWB): the level of anthropogenic carbon emissions per unit of human well-being. Here I examine how the effect of economic development on CIWB has changed since 1970 for 106 countries in multiple regional samples throughout the world. I find that early in this time period, increased development led to a reduction in CIWB for nations in Africa, but in recent decades the relationship has changed, becoming less sustainable. For nations in Asia and South and Central America, I find that development increases CIWB, and increasingly so throughout the 40-year period of study. The effect of development on CIWB for nations in the combined regions of North America, Europe and Oceania has remained positive, relatively larger than in other regions, and stable through time. Although future economic growth will probably improve human well-being throughout the world, this research suggests that it will also cost an increasing amount of carbon emissions. © 2014 Macmillan Publishers Limited.


Knight J.A.,University of Utah
Annals of Clinical and Laboratory Science | Year: 2012

A sedentary lifestyle is a very serious worldwide problem, especially in North America and Europe. Unfortunately, physical inactivity, which has progressively increased over the past several decades, significantly increases the risk of numerous diseases/disorders, including several forms of cancer, diabetes, hypertension, coronary and cerebrovascular diseases, overweight/obesity, and all-cause mortality, among others. Unless there is a reversal of this sedentary lifestyle, the incidence of these diseases/disorders will increase, life expectancy will decrease, and medical costs will continue to rise. © 2012 by the Association of Clinical Scientists, Inc.


Marx C.M.,University of Utah
American Journal of Managed Care | Year: 2013

Diabetes mellitus (DM) is a complex and progressive disease associated with significant morbidity and mortality. Both the prevalence and economic burden associated with DM have been steadily increasing and are projected to continue to increase. A series of cost reports published by the American Diabetes Association (ADA) between 1997 and 2012 have suggested that direct medical costs are the primary cost driver in DM. Direct costs have increased over 5-fold during this time frame, from $44 billion to $176 billion annually, likely due to both the increased prevalence of DM and increased costs of providing DM-related care. Trends in anti-diabetic medication usage as reported by Centers for Disease Control data from 1997 to 2011 have found that the proportion of diagnosed patients treated for DM has remained fairly stable. However, there has been an increase in the use of oral agents alone, a decrease in patients on insulin only, and a relatively small increase in the percentage of patients using both insulin and oral agents, suggesting stagnation regarding the uptake of insulin use. In parallel, the ADA cost and utilization data suggest that use of medications to treat DM-related comorbidities and complications has risen, which contributes to the risk of medication errors, avoidable adverse drug events, and noncompliance. These data highlight a few of the challenges involved in managing a population of patients with DM. A comprehensive assessment of unmet needs for the population with DM is essential for effective population management. An approach that strives to identify and reduce barriers to patients receiving optimal care and being active participants in their DM management will facilitate systemwide efforts to improve DM outcomes.


Botkin J.R.,University of Utah
Current Protocols in Human Genetics | Year: 2010

Genetic research often utilizes or generates information that is potentially sensitive to individuals, families, or communities. For these reasons, genetic research may warrant additional scrutiny from investigators and governmental regulators, compared to other types of biomedical research. The informed consent process should address the range of social and psychological issues that may arise in genetic research. This paper addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. Curr. Protoc. Hum. Genet. 66:1.16.1-1.16.13 © 2010 by John Wiley & Sons, Inc. Copyright © 2010 John Wiley & Sons, Inc.


Burgess E.W.,University of Alaska Fairbanks | Forster R.R.,University of Utah | Larsen C.F.,University of Alaska Fairbanks
Nature Communications | Year: 2013

Our poor understanding of tidewater glacier dynamics remains the primary source of uncertainty in sea level rise projections. On the ice sheets, mass lost from tidewater calving exceeds the amount lost from surface melting. In Alaska, the magnitude of calving mass loss remains unconstrained, yet immense calving losses have been observed. With 20% of the global new-water sea level rise coming from Alaska, partitioning of mass loss sources in Alaska is needed to improve sea level rise projections. Here we present the first regionally comprehensive map of glacier flow velocities in Central Alaska. These data reveal that the majority of the regional downstream flux is constrained to only a few coastal glaciers. We find regional calving losses are 17.1 Gt a-1, which is equivalent to 36% of the total annual mass change throughout Central Alaska. © 2013 Macmillan Publishers Limited. All rights reserved.


Roy N.,University of Utah
International Journal of Speech-Language Pathology | Year: 2012

Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal doseresponse relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible " overdosing". © 2012 The Speech Pathology Association of Australia Limited.


π-conjugated polymers find a range of applications in electronic devices. These materials are generally highly disordered in terms of chain length and chain conformation, besides being influenced by a variety of chemical and physical defects. Although this characteristic can be of benefit in certain device applications, disorder severely complicates materials analysis. Accurate analytical techniques are, however, crucial to optimising synthetic procedures and assessing overall material purity. Fortunately, single-molecule spectroscopic techniques have emerged as an unlikely but uniquely powerful approach to unraveling intrinsic material properties from the bottom up. Building on the success of such techniques in the lifo sciences, singlemolecule spectroscopy is finding increasing applicability in materials science, effectively enabling the dissection of the bulk down to the level of the individual molecular constituent This article reviews recent progress in singlemolecule spectroscopy of conjugated polymers as used in organic electronics. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.


Lessnick S.L.,University of Utah | Ladanyi M.,Sloan Kettering Cancer Center
Annual Review of Pathology: Mechanisms of Disease | Year: 2012

Approximately one-third of sarcomas contain specific translocations. Ewing sarcoma is the prototypical member of this group of sarcomas; it was the first to be recognized pathologically as a singular entity and to have its signature translocation defined cytogenetically, which led to the identification of its key driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeric transcription factor. We review recent progress in selected areas of Ewing sarcoma research, including the application of genome-wide chromatin immunoprecipitation analyses, to provide a comprehensive view of the EWS-FLI1 target gene repertoire, the identification of EWS-FLI1 target genes that may also point to therapeutically targetable pathways, and data from model systems as they relate to the elusive cell of origin of Ewing sarcoma and its possible similarities to mesenchymal stem cells. Copyright ©2012 by Annual Reviews. All rights reserved.


McAllister J.P.,University of Utah
Seminars in Fetal and Neonatal Medicine | Year: 2012

The pathophysiology of congenital and neonatal hydrocephalus is not well understood although the prognosis for patients with this disorder is far from optimal. A major obstacle to advancing our knowledge of the causes of this disorder and the cellular responses that accompany it is the multifactorial nature of hydrocephalus. Not only is the epidemiology varied and complex, but the injury mechanisms are numerous and overlapping. Nevertheless, several conclusions can be made with certainty: the age of onset strongly influences the degree of impairment; injury severity is dependent on the magnitude and duration of ventriculomegaly; the primary targets are periventricular axons, myelin, and microvessels; cerebrovascular injury mechanisms are prominent; gliosis and neuroinflammation play major roles; some but not all changes are preventable by draining cerebrospinal fluid with shunts and third ventriculostomies; cellular plasticity and physiological compensation probably occur but this is a major under-studied area; and pharmacologic interventions are promising. Rat and mouse models have provided important insights into the pathogenesis of congenital and neonatal hydrocephalus. Ependymal denudation of the ventricular lining appears to affect the development of neural progenitors exposed to cerebrospinal fluid, and alterations of the subcommissural organ influence the patency of the cerebral aqueduct. Recently these impairments have been observed in patients with fetal-onset hydrocephalus, so experimental findings are beginning to be corroborated in humans. These correlations, coupled with advanced genetic manipulations in animals and successful pharmacologic interventions, support the view that improved treatments for congenital and neonatal hydrocephalus are on the horizon. © 2012 Elsevier Ltd.


The question of the kinds of water bodies federal and state agencies may regulate under the federal Clean Water Act (CWA) has reached the US Supreme Court 3 times without clear resolution. The Waters of the United States (WOTUS) rule adopted by the Environmental Protection Agency and the Army Corps of Engineers (collectively, the agencies), based in part on a recent synthesis of science regarding the connectivity of surface waters (USEPA 2015), seeks to reduce regulatory uncertainty by clarifying which waters are subject to CWA regulation. The rule makes progress in that regard, but has been challenged in court on grounds that the agencies seek jurisdiction over waters that are not properly covered in the CWA, and members of Congress have taken steps to overturn the rule legislatively. The rule's legality depends on: 1) the breadth of federal constitutional authority over "navigable" waters, 2) the text and meaning of the CWA, and 3) the relationship between the proposed regulation and the science used by the agencies to support the rule. From a constitutional perspective, the courts will have to determine whether the agencies have demonstrated that the waters over which jurisdiction is asserted have a sufficient effect on traditional navigable waters to be subject to federal regulation under the Commerce Clause of the US Constitution. From a statutory perspective, the courts will have to determine whether the scientific evidence shows that those types of water bodies fall within the intent and scope of the CWA as adopted by Congress. From a scientific perspective, to defend the rule in court the agencies will have to show that the synthesis report and other relevant scientific information adequately demonstrate that regulation of various categories of upstream waters is necessary to ensure protection of traditional navigable waters over which the agencies clearly have regulatory authority, and other types of waters over which the agencies have jurisdiction under the Constitution and the text of the CWA. © 2015 by The Society for Freshwater Science.


Rapoport N.,University of Utah
International Journal of Hyperthermia | Year: 2012

During the last decade, nanomedicine has emerged as a new field of medicine that utilises nanoscale materials for delivery of drugs, genes and imaging agents. The efficiency of drug delivery may be enhanced by the application of directed energy, which provides for drug targeting and enhanced intracellular uptake. In this paper, we present a review of recent advances in the ultrasound-mediated drug delivery with the emphasis on polymeric micelles as tumour-targeted drug carriers. This new modality of drug targeting to tumours is based on the drug encapsulation in polymeric micelles followed by a localised release at the tumour site triggered by focused ultrasound. The rationale behind this approach is that drug encapsulation in micelles decreases systemic concentration of free drug and provides for a passive drug targeting to tumours via the enhanced permeability and retention (EPR) effect, therefore reducing unwanted drug interactions with healthy tissues. Ultrasound affects micellar drug delivery on various levels. Mild hyperthermia induced by ultrasound may enhance micelle extravasation into tumour tissue; mechanical action of ultrasound results in drug release from micelles and enhances the intracellular uptake of both released and encapsulated drug. In addition, polymeric micelles sensitise multidrug resistant (MDR) cells to the action of drugs. © 2012 Informa UK Ltd All rights reserved.


Sekercioglu C.H.,University of Utah
Journal of Ornithology | Year: 2012

Although most bird species avoid agricultural areas, nearly a third of all birds regularly to occasionally use such habitats, often providing important ecosystem services like pest control, pollination, and seed dispersal. Combining literature review with large-scale analyses of the ecological characteristics of the world's birds, I compared tropical bird species that prefer forests, agricultural areas or both, with respect to body mass, diet, range and population size, frequency, conservation status, habitat and resource specialization. Compared to primary forests, species richness of large frugivorous and insectivorous birds (especially terrestrial and understorey species) often declines in agroforests. In contrast, nectarivores, small-to-medium insectivores (especially migrants and canopy species), omnivores, and sometimes granivores and small frugivores do better, frequently by tracking seasonal resources. However, changes in guild species numbers do not necessarily translate to changes in relative abundance, biomass or function, and more studies are needed to quantify these important measures. These findings indicate that the replacement of forests and agroforests with simplified agricultural systems can result in shifts towards less specialized bird communities with altered proportions of functional groups. These shifts can reduce avian ecosystem function and affect the ecosystem services provided by birds in agroforests and other agricultural landscapes. © 2012 Dt. Ornithologen-Gesellschaft e.V.


Silver R.M.,University of Utah
Seminars in Perinatology | Year: 2010

Most studies of cesarean morbidity focus on short term, rather than long term complications. However, women undergoing cesarean delivery are at increased risk for a chronic problems as well. These include pain and surgical adhesions, as well as a possible increased risk for infertility or sub-fertility and perinatal complications in subsequent pregnancies. The most serious risk for women undergoing multiple repeat cesarean deliveries is a dramatically increased risk for life threatening hemorrhage and morbidity in the setting of placenta accreta. This chapter outlines these long term risks of cesarean delivery so that they may be factored into the risk:benefit ratio for women considering vaginal birth after cesarean delivery (VBAC). © 2010 Elsevier Inc.


Wan N.,University of Utah
Applied Geography | Year: 2015

Exposure to agricultural pesticides has been linked with a variety of public health problems. However, such investigations were generally restricted by inadequate exposure information and small study areas. This article presents a GIS approach to generate objective information of population exposure to specific pesticide ingredients for large areas. Specifically, it integrates land use information that was derived from remote sensing images, population grid data, and county level pesticide usage data to model residential exposure to pesticides for the entire state of Nebraska. Using Atrazine as an example, this study demonstrated how to derive useful indicators of pesticide exposure based on the proposed method and how to up-scale the information to area levels to match up with public health datasets. The spatial pattern of exposure to Atrazine in Nebraska was also examined and discussed. This approach has great potential for assessing exposure to different pesticide ingredients in environment-health studies. © 2014 Elsevier Ltd.


Sekercioglu C.H.,University of Utah
Science | Year: 2011

Researchers have documented how the loss of pollinating birds affects a plant that depends on them.


Jones D.,University of Utah
Behavioral and Brain Sciences | Year: 2010

Research in anthropology has shown that kin terminologies have a complex combinatorial structure and vary systematically across cultures. This article argues that universals and variation in kin terminology result from the interaction of (1) an innate conceptual structure of kinship, homologous with conceptual structure in other domains, and (2) principles of optimal, grammatical communication active in language in general. Kin terms from two languages, English and Seneca, show how terminologies that look very different on the surface may result from variation in the rankings of a universal set of constraints. Constraints on kin terms form a system: some are concerned with absolute features of kin (sex), others with the position (distance and direction) of kin in kinship space, others with groups and group boundaries (matrilines, patrilines, generations, etc.). Also, kin terms sometimes extend indefinitely via recursion, and recursion in kin terminology has parallels with recursion in other areas of language. Thus the study of kinship sheds light on two areas of cognition, and their phylogeny. The conceptual structure of kinship seems to borrow its organization from the conceptual structure of space, while being specialized for representing genealogy. And the grammar of kinship looks like the product of an evolved grammar faculty, opportunistically active across traditional domains of semantics, syntax, and phonology. Grammar is best understood as an offshoot of a uniquely human capacity for playing coordination games. © 2010 Cambridge University Press.


Wei Y.D.,University of Utah
Applied Geography | Year: 2015

Spatial inequality has drawn renewed scholarly interests and societal concerns. This paper reviews the literature on regional inequality, with a focus on spatiality of regional economic/income inequality, to make a timely contribution for a better understanding of the complexity and dynamics of spatial inequality. We find that existing theories disagree over temporal trends and underlying forces of regional inequality, and spatio-temporal models have been favored by economic geographers. It also shows that the research on regional inequality covers all continents of the world, including both developed and developing countries. The scope of research has also been broadened, expanding to household and environmental inequalities. The paper proposes components of spatiality of regional inequality, including scale, location, physical geography, place, space, spatial network, and spatial-temporal models. The paper also proposes areas for future research. © 2015 Elsevier Ltd.


The primary motivation of the present investigation stems from the need for understanding the three-dimensional singular stress fields in the vicinity of the re-entrant circumferential bimaterial junction corner line between a thin film island and the underlying substrate, either free-standing or fully/partially bonded to a super-rigid block. A three-dimensional eigenfunction expansion approach is employed for determination of the singular stress field in the vicinity of the re-entrant circumferential bimaterial junction corner line. The island-substrate bimaterial system is subjected to extension/bending (mode I), shear/twisting (mode II) and torsional (mode III) far field loadings. Both the island and substrate materials are assumed to be isotropic and elastic. The boundary conditions, prescribed on either side of the interfacial bond line between the island and substrate materials (free-free, fixed-fixed, free-fixed and fixed-free), are exactly satisfied. Numerical results include the dependence of the lowest eigenvalue(s) (or most severe order(s) of stress singularity) on the wedge aperture angle of the island material (looking at a axisymmetric cross-section). Variation of the same with respect to the shear moduli ratio of the constituent island and substrate materials is also an important part of the present investigation. Hitherto unobserved interesting and physically meaningful conclusions in regards to the mixed free-fixed type singularity and delamination type flaw sensitivity of an island-substrate bimaterial system are also presented. © 2013 Elsevier Ltd.


Jones K.B.,University of Utah
Sarcoma | Year: 2011

Osteosarcoma remains a deadly malignancy afflicting adolescents and young adults. The lack of a precursor and the panoply of genetic aberrations present in identified osteosarcomas makes study of its initiation difficult. A number of candidate hypotheses have been tested in the mouse, a species with a higher background incidence of osteosarcoma. Chemical carcinogens, external beam radiation, and bone-seeking heavy metal radioisotopes have all proven to be osteosarcomagenic in wild-type mice. A number of oncogenes, introduced via integrating viruses or aberrantly activated from heritable genetic loci, participate in and can individually drive osteosarcomagenesis. Germline and conditional gene ablations in the form of some but not all aneuploidy-inducing genes, conventional tumor suppressors, and factors that function normally in mesenchymal differentiation have also proven osteosarcomagenic, especially in combinations that silence the Rb1 and p53 pathways. This paper reviews the rich history of mouse models of osteosarcomagenesis, what they have taught us about the human disease, and what future mouse experiments yet promise to teach. Copyright © 2011 Kevin B. Jones.


Chronic inflammatory demyelinating polyradicoloneuropathy (CIDP) is a treatable form of neuropathy. Efforts to devise sets of electrodiagnostic (nerve conduction) criteria to distinguish primary demyelination from primary axonal neuropathies have been elusive, and at least 16 criteria have been proposed. Modifications to criteria frequently represent minor changes based on applying a set to a small number of patients with the clinical diagnosis of CIDP, whereas others are based on physiological changes related to demyelination and other pathophysiological features. The various modifications continue to result in limited sensitivity, likely related to the wide range of nerve conduction abnormalities among CIDP patients. Although some sets are appropriate for formal clinical drug trials, their complexity makes them difficult to apply in the clinic or electromyography laboratory. This study considers the evolution of the criteria, discusses their limitations, and ends with a simplified set of guidelines that can be applied in the clinic or laboratory. © 2011 Wiley Periodicals, Inc.


Quinn R.,University of Utah
American Journal of Public Health | Year: 2013

Policy leaders and public health experts may be overlooking effective ways to stimulate innovative antibiotic research and development. I analyzed archival resources concerning the US government's efforts to produce penicillin during World War II, which demonstrate how much science policy can differ from present approaches. By contrast to current attempts to invigorate commercial participation in antibiotic development, the effort to develop the first commercially produced antibiotic did not rely on economic enticements or the further privatization of scientific resources. Rather, this extremely successful scientific and, ultimately, commercial endeavor was rooted in government stewardship, intraindustry cooperation, and the open exchange of scientific information. For policymakers facing the problem of stimulating antibiotic research and development, the origins of the antibiotic era offer a template for effective policy solutions that concentrate primarily on scientific rather than commercial goals.


Universal bounds on the electrical and elastic response of two-phase (and multiphase) ellipsoidal or parallelopipedic bodies have been obtained by Nemat-Nasser and Hori. Here we show how their bounds can be improved and extended to bodies of arbitrary shape. Although our analysis is for two-phase bodies with isotropic phases it can easily be extended to multiphase bodies with anisotropic constituents. Our two-phase bounds can be used in an inverse fashion to bound the volume fractions occupied by the phases, and when the volume fraction is asymptotically small reduce to those of Capdeboscq and Vogelius, for electrical conductivity, and Capdeboscq and Kang, for elasticity. Other volume fraction bounds derived here utilize information obtained from thermal, magnetic, dielectric or elastic responses. One bound on the volume fraction can be obtained by simply immersing the body in a water filled cylinder with a piston at one end and measuring the change in water pressure when the piston is displaced by a known small amount. This bound may be particularly effective for estimating the volume of cavities in a body. We also obtain new bounds utilizing just one pair of (voltage, flux) electrical measurements at the boundary of the body. © 2011 Elsevier Ltd. All rights reserved.


Del Fiol G.,University of Utah | Workman T.E.,Lister Hill Center | Gorman P.N.,Oregon Health And Science University
JAMA Internal Medicine | Year: 2014

IMPORTANCE In making decisions about patient care, clinicians raise questions and are unable to pursue or find answers to most of them. Unanswered questions may lead to suboptimal patient care decisions. OBJECTIVE To systematically review studies that examined the questions clinicians raise in the context of patient care decision making. DATA SOURCES MEDLINE (from 1966), CINAHL (from 1982), and Scopus (from 1947), all through May 26, 2011. STUDY SELECTION Studies that examined questions raised and observed by clinicians (physicians, medical residents, physician assistants, nurse practitioners, nurses, dentists, and care managers) in the context of patient care were independently screened and abstracted by 2 investigators. Of 21 710 citations, 72 met the selection criteria. DATA EXTRACTION AND SYNTHESIS Question frequencywas estimated by pooling data from studies with similar methods. MAIN OUTCOMES AND MEASURES Frequency of questions raised, pursued, and answered and questions by type according to a taxonomy of clinical questions. Thematic analysis of barriers to information seeking and the effects of information seeking on decision making. RESULTS In 11 studies, 7012 questions were elicited through short interviews with clinicians after each patient visit. The mean frequency of questions raised was 0.57 (95%CI, 0.38-0.77) per patient seen, and clinicians pursued 51%(36%-66%) of questions and found answers to 78%(67%-88%) of those they pursued. Overall, 34%of questions concerned drug treatment, and 24%concerned potential causes of a symptom, physical finding, or diagnostic test finding. Clinicians' lack of time and doubt that a useful answer exists were the main barriers to information seeking. CONCLUSIONS AND RELEVANCE Clinicians frequently raise questions about patient care in their practice. Although they are effective at finding answers to questions they pursue, roughly half of the questions are never pursued. This picture has been fairly stable over time despite the broad availability of online evidence resources that can answer these questions. Technology-based solutions should enable clinicians to track their questions and provide just-in-time access to high-quality evidence in the context of patient care decision making. Opportunities for improvement include the recent adoption of electronic health record systems and maintenance of certification requirements. © 2014 American Medical Association. All rights reserved.


Patel S.,University of Utah
American journal of obstetrics and gynecology | Year: 2014

OBJECTIVE: Delayed umbilical cord clamping benefits extremely low gestational age neonates (ELGANs) but has not gained wide acceptance. We hypothesized that milking the umbilical cord (MUC) would avoid resuscitation delay but improve hemodynamic stability and reduce rates for composite outcome of severe intraventricular hemorrhage, necrotizing enterocolitis, and/or death before discharge.STUDY DESIGN: We implemented a joint neonatal/maternal-fetal quality improvement process for MUC starting September 2011. The MUC protocol specified that infants who were born at <30 weeks of gestation undergo MUC 3 times over a duration of <30 seconds at delivery. Obstetric and neonatal data were collected until discharge. We compared the MUC group to retrospective ELGAN cohort delivered at our center between January 2010 and August 2011. Analysis was intention-to-treat.RESULTS: We identified 318 ELGANs: 158 eligible for MUC and 160 retrospective control neonates. No adverse events were reported with cord milking. There was no difference in neonatal resuscitation, Apgar scores, or admission temperature. Hemodynamic stability was improved in the MUC group with higher mean blood pressures through 24 hours of age, despite less vasopressor use (18% vs 32%; P < .01). The initial hematocrit value was higher (50% vs 45%; P < .01), and red cell transfusions were fewer (57% vs 79%; P < .01) in MUC vs control infants. Presence of the composite outcome was significantly less in MUC vs the historic control infants (22% v 39%; odds ratio, 1.81; 95% confidence interval, 1.06-3.10). There were also reductions in intraventricular hemorrhage, necrotizing enterocolitis, and death before hospital discharge.CONCLUSION: MUC improves early hemodynamic stability and is associated with lower rates of serious morbidity and death among ELGANs. Copyright © 2014 Elsevier Inc. All rights reserved.


A three-dimensional eigenfunction expansion technique, based in part on separation of the thickness variable and partly utilizing a modified Frobenius-type series expansion in conjunction with the Eshelby-Stroh formalism, is used to compute the local stress singularity, in the vicinity of a kinked fibre/matrix trimaterial junction front, representing a measure of the degree of inherent flaw sensitivity of unidirectional carbon-fibre-reinforced composites under compression. Micro-kinking, more prominent in the misaligned regions of carbon fibres, is caused by crystallite disorientations, as detected by the Raman and X-ray measurements, as well as dislocation glide in crystallites and intra/intercrystallite disorders. The present analysis explains the test results relating to propagation of failure from such discontinuities in a unidirectional composite under compression. Numerical results presented include the effect of fibre wedge aperture angle on the strengths of the mode I and mode II singularities. Of special practical interest is the comparison of the inherent flaw sensitivity of carbon/epoxy and glass/epoxy composites, because improvement of the compressive strength and kink toughness was earlier accomplished through commingling of highly anisotropic (and crystalline) carbon and isotropic (and amorphous) glass fibres at the tow level. Compression fracture of these composites can be fully explained and quantified by the present three-dimensional linear elastic stress singularity analysis-based method. Finally, numerical results, pertaining to the through-thickness variation of stress intensity factor for symmetric uniform load and its skew-symmetric counterpart that also satisfies the boundary conditions on the top and bottom surfaces of a compressed composite monolayer, in the vicinity of a trimaterial junction front, are also presented. © 2014 © 2014 Taylor & Francis.


Garrett T.J.,University of Utah
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012

Regardless of a system's complexity or scale, its growth can be considered to be a spontaneous thermodynamic response to a local convergence of down-gradient material flows. Here it is shown how system growth can be constrained to a few distinct modes that depend on the time integral of past flows and the current availability of material and energetic resources. These modes include a law of diminishing returns, logistic behaviour and, if resources are expanding very rapidly, super-exponential growth. For a case where a system has a resolved sink as well as a source, growth and decay can be characterized in terms of a slightly modified form of the predator-prey equations commonly employed in ecology, where the perturbation formulation of these equations is equivalent to a damped simple harmonic oscillator. Thus, the framework presented here suggests a common theoretical under-pinning for emergent behaviours in the physical and life sciences. Specific examples are described for phenomena as seemingly dissimilar as the development of rain and the evolution of fish stocks. © 2012 The Royal Society.


Gondolo P.,University of Utah
Nuclear Data Sheets | Year: 2014

Astronomical observations from small galaxies to the largest scales in the universe can be consistently explained by the simple idea of dark matter. The nature of dark matter is however still unknown. Empirically it cannot be any of the known particles, and many theories postulate it as a new elementary particle. Searches for dark matter particles are under way: production at high-energy accelerators, direct detection through dark matter-nucleus scattering, indirect detection through cosmic rays, gamma rays, or effects on stars. Particle dark matter searches rely on observing an excess of events above background, and a lot of controversies have arisen over the origin of observed excesses. With the new high-quality cosmic ray measurements from the AMS-02 experiment, the major uncertainty in modeling cosmic ray fluxes is in the nuclear physics cross sections for spallation and fragmentation of cosmic rays off interstellar hydrogen and helium. The understanding of direct detection backgrounds is limited by poor knowledge of cosmic ray activation in detector materials, with order of magnitude differences between simulation codes. A scarcity of data on nucleon spin densities blurs the connection between dark matter theory and experiments. What is needed, ideally, are more and better measurements of spallation cross sections relevant to cosmic rays and cosmogenic activation, and data on the nucleon spin densities in nuclei. © 2014 Elsevier Inc.


A computational procedure is developed to determine initial instabilities within a three-dimensional laminar boundary layer and to follow these instabilities in the streamwise direction through to the resulting intermittency exponents within a fully developed turbulent flow. The fluctuating velocity wave vector component equations are arranged into a Lorenz-type system of equations. The nonlinear time series solution of these equations at the fifth station downstream of the initial instabilities indicates a sequential outward burst process, while the results for the eleventh station predict a strong sequential inward sweep process. The results for the thirteenth station indicate a return to the original instability autogeneration process. The nonlinear time series solutions indicate regions of order and disorder within the solutions. Empirical entropies are defined from decomposition modes obtained from singular value decomposition techniques applied to the nonlinear time series solutions. Empirical entropic indices are obtained from the empirical entropies for two streamwise stations. The intermittency exponents are then obtained from the entropic indices for these streamwise stations that indicate the burst and autogeneration processes. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Ellis R.E.,Rowan University | Stanfield G.M.,University of Utah
Seminars in Cell and Developmental Biology | Year: 2014

In the nematode C. elegans, both males and self-fertile hermaphrodites produce sperm. As a result, researchers have been able to use a broad range of genetic and genomic techniques to dissect all aspects of sperm development and function. Their results show that the early stages of spermatogenesis are controlled by transcriptional and translational processes, but later stages are dominated by protein kinases and phosphatases. Once spermatids are produced, they participate in many interactions with other cells - signals from the somatic gonad determine when sperm activate and begin to crawl, signals from the female reproductive tissues guide the sperm, and signals from sperm stimulate oocytes to mature and be ovulated. The sperm also show strong competitive interactions with other sperm and oocytes. Some of the molecules that mediate these processes have conserved functions in animal sperm, others are conserved proteins that have been adapted for new roles in nematode sperm, and some are novel proteins that provide insights into evolutionary change. The advent of new techniques should keep this system on the cutting edge of research in cellular and reproductive biology. © 2014 Elsevier Ltd.


Carroll D.,University of Utah
Annual Review of Biochemistry | Year: 2014

Current technology enables the production of highly specific genome modifications with excellent efficiency and specificity. Key to this capability are targetable DNA cleavage reagents and cellular DNA repair pathways. The break made by these reagents can produce localized sequence changes through inaccurate nonhomologous end joining (NHEJ), often leading to gene inactivation. Alternatively, user-provided DNA can be used as a template for repair by homologous recombination (HR), leading to the introduction of desired sequence changes. This review describes three classes of targetable cleavage reagents: zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas RNA-guided nucleases (RGNs). As a group, these reagents have been successfully used to modify genomic sequences in a wide variety of cells and organisms, including humans. This review discusses the properties, advantages, and limitations of each system, as well as the specific considerations required for their use in different biological systems. Copyright © 2014 by Annual Reviews. All rights reserved.


Sanguinetti M.C.,University of Utah
Pflugers Archiv European Journal of Physiology | Year: 2010

Human ether a go-go-related gene type 1 (hERG1) K+ channels conduct the rapid delayed rectifier K+ current and mediate action potential repolarization in the heart. Mutations in KCNH2 (the gene that encodes hERG1) causes LQT2, one of the most common forms of long QT syndrome, a disorder of cardiac repolarization that predisposes affected subjects to ventricular arrhythmia and increases the risk of sudden cardiac death. Hundreds of LQT2-associated mutations have been described, and most cause a loss of function by disrupting subunit folding, assembly, or trafficking of the channel to the cell surface. Loss-of-function mutations in hERG1 channels have also recently been implicated in epilepsy. A single gain-offunction mutation has been described that causes short QT syndrome and cardiac arrhythmia. In addition, up-regulation of hERG1 channel expression has been demonstrated in specific tumors and has been associated with skeletal muscle atrophy in mice. © Springer-Verlag 2009.


Garrido-Laguna I.,University of Utah | Hidalgo M.,Gastrointestinal Cancer Clinical Research Unit
Nature Reviews Clinical Oncology | Year: 2015

Pancreatic cancer is expected to be the second deadliest malignancy in the USA by 2020. The survival rates for patients with other gastrointestinal malignancies have increased consistently during the past 30 years; unfortunately, however, the outcomes of patients with pancreatic cancer have not changed significantly. Although surgery remains the only curative treatment for pancreatic cancer, therapeutic strategies based on initial resection have not substantially improved the survival of patients with resectable disease over the past 25 years; presently, more than 80% of patients suffer disease relapse after resection. Preclinical evidence that pancreatic cancer is a systemic disease suggests a possible benefit for early administration of systemic therapy in these patients. In locally advanced disease, the role of chemoradiotherapy is increasingly being questioned, particularly considering the results of the LAP-07 trial. Novel biomarkers are clearly needed to identify subsets of patients likely to benefit from chemoradiotherapy. In the metastatic setting, FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin), and nab-paclitaxel plus gemcitabine have yielded only modest improvements in survival. Thus, new treatments are urgently needed for patients with pancreatic cancer. Herein, we review the state-of-the-art of pancreatic cancer treatment, and the upcoming novel therapeutics that hold promise in this disease are also discussed. © 2015 Macmillan Publishers Limited. All rights reserved.


Hartnett M.E.,University of Utah | Penn J.S.,Vanderbilt University
New England Journal of Medicine | Year: 2012

Models of oxygen-induced retinopathy have elucidated how oxygen stresses may lead to the development of retinopathy of prematurity through activated signaling pathways. Screening is currently carried out according to the guidelines in Table 1. Current treatment for severe retinopathy of prematurity focuses on laser therapy and visual rehabilitation, and potential new treatment strategies include targets within oxidative pathways, erythropoietin, and anti-VEGF agents. Copyright © 2012 Massachusetts Medical Society.


Condic M.L.,University of Utah
Stem Cells and Development | Year: 2014

There is surprising confusion surrounding the concept of biological totipotency, both within the scientific community and in society at large. Increasingly, ethical objections to scientific research have both practical and political implications. Ethical controversy surrounding an area of research can have a chilling effect on investors and industry, which in turn slows the development of novel medical therapies. In this context, clarifying precisely what is meant by "totipotency" and how it is experimentally determined will both avoid unnecessary controversy and potentially reduce inappropriate barriers to research. Here, the concept of totipotency is discussed, and the confusions surrounding this term in the scientific and nonscientific literature are considered. A new term, "plenipotent," is proposed to resolve this confusion. The requirement for specific, oocyte-derived cytoplasm as a component of totipotency is outlined. Finally, the implications of twinning for our understanding of totipotency are discussed. © Copyright 2014, Mary Ann Liebert, Inc.


Visinelli L.,University of Utah
Journal of Cosmology and Astroparticle Physics | Year: 2011

We derive the requirements that a generic axion-like field has to satisfy in order to play the role of the inflaton field in the warm inflation scenario. Compared to the parameter space in ordinary Natural Inflation models, we find that the parameter space in our model is enlarged. In particular, we avoid the problem of having an axion decay constant f that relates to the Planck scale, which is instead present in the ordinary Natural Inflation models; in fact, our model can easily accommodate values of the axion decay constant that lie well below the Planck scale. © 2011 IOP Publishing Ltd and SISSA.


Cheatham III T.E.,University of Utah | Case D.A.,Rutgers University
Biopolymers | Year: 2013

We present a brief, and largely personal, history of computer simulations of DNA and RNA oligonucleotides, with an emphasis on duplex structures and the Amber force fields. Both explicit and implicit solvent models are described, and methods for estimating structures, thermodynamics and mechanical properties of duplexes are illustrated. This overview, covering about two decades of work, provides a perspective for a discussion of prospects and obstacles for future simulations of RNA and DNA. Copyright © 2013 Wiley Periodicals, Inc.


Kiefer J.C.,University of Utah
Developmental Dynamics | Year: 2011

Gene targeting in mice, first reported 25 years ago, has led to monumental advances in the understanding of basic biology and human disease. The ability to employ a similarly straightforward method for gene manipulation in other experimental organisms would make their already significant contributions all the more powerful. Here, we briefly outline the strengths and weaknesses of reverse genetics techniques in non-murine model organisms, ending with a more detailed description of two that promise to bring targeted gene modification to the masses: zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Dana Caroll, a forefather of zinc finger technology, and Bo Zhang, among the first to introduce TALEN-targeted mutagenesis to zebrafish, discuss their experience with these techniques, and speculate about the future of the field. © 2011 Wiley Periodicals, Inc.


Guo F.,University of Alabama at Birmingham | He D.,University of Utah | Zhang W.,University of Alabama at Birmingham | Walton R.G.,University of Kentucky
Journal of the American College of Cardiology | Year: 2012

Objectives: The purpose of this study was to quantify the trends in blood pressure (BP), and the prevalence, awareness, management, and control of hypertension in U.S. adults (<20 years of age) from 1999 to 2010, and to assess the efficacy of current clinical measures in diagnosing and adequately treating hypertensive patients. Background: Hypertension is a major independent risk factor for cardiovascular disease and stroke. Recent data indicate a decreasing trend in hypertension prevalence, along with improvements in hypertension awareness, management, and control. Methods: The study used regression models to assess the trends in hypertension prevalence, awareness, management, and control from 1999 to 2010 among 28,995 male and female adults with BP measurements from a nationally representative sample of the noninstitutionalized U.S. population (National Health and Nutrition Examination Survey [NHANES] 1999 to 2010), with special attention given to 5,764 participants in NHANES 2009 to 2010. Results: In 2009 to 2010, the prevalence of hypertension was 30.5% among men and 28.5% among women. The hypertension awareness rate was 69.7% (95% confidence interval [CI]: 62.0% to 77.4%) among men and 80.7% (95% CI: 74.5% to 86.8%) among women. The hypertension control rate was 40.3% (95% CI: 33.7% to 46.9%) for men and 56.3% (95% CI: 49.2% to 63.3%) for women. From 1999 to 2010, the prevalence of hypertension remained stable. Although hypertension awareness, management, and control improved, the overall rates remained poor (74.0% for awareness, 71.6% for management, 46.5% for control, and 64.4% for control in management); worse still, no improvement was shown from 2007 to 2010. Conclusions: From 1999 to 2010, prevalence of hypertension remained stable. Hypertension awareness, management, and control were improved, but remained poor; nevertheless, there has been no improvement since 2007. © 2012 American College of Cardiology Foundation.


Steady state transport through mixed proton, oxygen ion and electron/hole conductors is examined in fuel cell, driven fuel cell, and electrolyzer modes. Oxygen ion and proton current densities and the corresponding effective permeation fluxes of H 2 and O 2 obey Onsager equations. Chemical potentials of electrically neutral species, μH 2andμ O 2 in the electrolyte are determined in terms of transport parameters and operating conditions. In fuel cell mode μH 2andμO 2 in the electrolyte are bounded by electrode values. However, in electrolyzer and driven fuel cell modes, μH 2andμO 2 in the electrolyte need not be bounded by electrode values. Under some conditions μH 2andμO 2 in the electrolyte exceed electrolyte thermodynamic stability leading to device failure. The analysis shows that from the standpoint of stability, electrolytes exhibiting mixed ionic-electronic conducting properties with large interfacial electron transfer resistances are preferred over predominantly ionic conducting materials. © 2012 Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.


Roy N.,University of Utah
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2010

Purpose of Review: Muscle tension dysphonia (MTD) can mimic the voice features of adductor spasmodic dysphonia (ADSD) leading to diagnostic confusion. Researchers have begun to compare characteristics of MTD and ADSD to determine whether there are markers which reliably distinguish the two disorders and lead to improved differential diagnosis. Recent Findings: Differences between MTD and ADSD have been identified during fiberoptic laryngoscopy, phonatory airflow measurement, acoustic analysis, and variable sign expression based upon phonatory task. In general, evidence of task-dependent sign expression and intraword phonatory breaks should raise suspicion of ADSD over MTD. However, on the basis of conventional standards of diagnostic precision, no single diagnostic test currently exists that reliably distinguishes the two disorders. Summary: Although perceptual voice evaluation remains the standard for differential diagnosis of ADSD and MTD, knowledge of factors that influence the severity of sign expression in ADSD is important to differential diagnosis. During clinical assessment, voice clinicians who use generic stimulus materials that do not control for specific phonetic environments or voice tasks may miss critical phenomenological features of ADSD. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Werner L.,University of Utah | Werner L.,Berlin Eye Research Institute
Journal of Cataract and Refractive Surgery | Year: 2010

Glistenings are fluid-filled microvacuoles that form within the intraocular lens (IOL) optic when the IOL is in an aqueous environment. They are observed in all types of IOLs but have been mainly associated with hydrophobic acrylic IOLs. Experimental and clinical studies suggest the various hydrophobic acrylic IOLs on the market exhibit different tendencies toward glistenings. Factors influencing glistening formation include IOL material composition, manufacturing technique, packaging, associated conditions such as glaucoma or those leading to breakdown of the blood-aqueous barrier, as well as concurrent use of ocular medications. Although the impact of glistenings on postoperative visual function and the evolution of glistenings in the late postoperative period remain controversial, IOL explantation has rarely been reported. The phenomenon of surface light scattering has also been described in association with hydrophobic acrylic IOLs. Its mechanism of formation is controversial but may be related to long-term phase separation water near the IOL surface, although not seen as microvacuoles. © 2010 ASCRS and ESCRS.


A novel eigenfunction expansion technique, based in part on separation of the thickness variable, is developed to derive three-dimensional asymptotic stress fields in the vicinity of the front of a semi-infinite through-crack weakening an infinite plate made of a homogeneous cubic single crystal. Crack-side boundary conditions and those that are prescribed on the top and bottom (free) surfaces of the cubic crystal plate are exactly satisfied. Explicit expressions for singular stress fields in the vicinity of the front of through-thickness cracks, weakening cubic single crystal plates subjected to far-field extension/bending (mode I), sliding shear/twisting (mode II) and antiplane shear (mode III) loadings are presented. The present investigation considers three through-crack systems (crack plane)[crack front] [propagation direction], (010)[001] [100], [image omitted] and [image omitted], weakening cubic crystals, and their relatively easier cleavage planes for propagation. It also introduces a new concept of lattice crack deviation (LCD) barrier, which can explain the reported discrepancy between simulations and experiments with regards to crack deviation from a difficult cleavage system to an easier one. Additionally, the relationships of the easier cleavage systems based on the present solutions with the structural chemistry aspects of various single crystals, such as bcc alkali metals, bcc transition alkali metals, fcc transition metals, group IVA (diamond cubic) elements, usually ionic compounds (rock salt and fluorite structures), covalent compounds (zinc blende structure), etc., are also discussed. Finally, the LCD parameter is strongly correlated with the anisotropic ratio for the cracked cubic crystal concerned. © 2010 Taylor & Francis.


Kohan D.E.,University of Utah | Pollock D.M.,University of Georgia
British Journal of Clinical Pharmacology | Year: 2013

Numerous pre-clinical studies have implicated endothelin-1 in the pathogenesis of diabetic and non-diabetic chronic kidney disease (CKD). Renal endothelin-1 production is almost universally increased in kidney disease. The pathologic effects of endothelin-1, including vasoconstriction, proteinuria, inflammation, cellular injury and fibrosis, are likely mediated by the endothelin A (ETA) receptor. ETA antagonism alone, and/or combined ETA/B blockade, reduces CKD progression. Based on the strong pre-clinical data, several clinical trials using ETA antagonists were conducted. Small trials involving acute intravenous endothelin receptor blockade suggest that ETA, but not ETB, blockade exerts protective renal and vascular effects in CKD patients. A large phase 3 trial (ASCEND) examined the effects of avosentan, an endothelin receptor antagonist, on renal disease progression in diabetic nephropathy. Proteinuria was reduced after 3-6months of treatment. However the study was terminated due to increased morbidity and mortality associated with avosentan-induced fluid retention. Several phase 2 trials using avosentan at lower doses than in ASCEND, atrasentan or sitaxsentan (the latter two being highly ETA-selective) showed reductions in proteinuria on top of renin-angiotensin system blockade. Infrequent and clinically insignificant fluid retention was observed at the most effective doses. Additional trials using ETA blockers are ongoing or being planned in patients with diabetic nephropathy or focal segmental glomerulosclerosis. Moving forward, such studies must be conducted with careful patient selection and attention to dosing in order to minimize adverse side effects. Nonetheless, there is cause for optimism that this class of agents will ultimately prove to be effective for the treatment of CKD. © 2012 The British Pharmacological Society.


Carey J.C.,University of Utah
Advances in Experimental Medicine and Biology | Year: 2010

Case reports are defined as the scientific documentation of a single clinical observation and have a time-honored and rich tradition in medicine and scientific publication. Case reports represent a relevant, timely, and important study design in advancing medical scientific knowledge especially of rare diseases.While there are clear limitations to the methodology of case studies in determination of treatment and establishment of new tests, the observation of a single patient can add to our understanding of etiology, pathogenesis, natural history, and treatment of particularly rare diseases, and to the training of potential junior investigators. In recent years this class of scientific publication has come under scrutiny and disfavor among some in the medical scientific publication community and case studies are frequently relegated to the lowest rung of the hierarchy of study design. In this chapter the author will review and summarize the debate around the scientific publication of case reports in the context of the study of rare diseases and will present a taxonomy that ideally will encourage further dialogue on the topic. Future research on the importance of case reports in advancing knowledge of rare diseases is recommended. © Springer Science+Business Media B.V. 2010.


Pavia A.T.,University of Utah
Annals of Internal Medicine | Year: 2013

On 31 March 2013, Chinese public health authorities notified the World Health Organization of the isolation of influenza A(H7N9) virus from 3 critically ill adults (1). This avian influenza virus had never before been detected in humans, and its association with severe disease electrified influenza experts. Could this foreshadow a pandemic? The cases generated many questions for public health authorities, influenza scientists, clinicians, and the public. Many remain to be answered, but the answers to 2 seem clear. © 2013 American College of Physicians.


Histone deacetylases 1 and 2 (HDAC1,2) belong to the class I HDAC family, which are targeted by the FDA-approved small molecule HDAC inhibitors currently used in cancer therapy. HDAC1,2 are recruited to DNA break sites during DNA repair and to chromatin around forks during DNA replication. Cancer cells use DNA repair and DNA replication as survival mechanisms and to evade chemotherapy- induced cytotoxicity. Hence, it is vital to understand how HDAC1,2 function during the genome maintenance processes (DNA replication and DNA repair) in order to gain insights into the mode-of-action of HDAC inhibitors in cancer therapeutics. The first-in-class HDAC1,2-selective inhibitors and Hdac1,2 conditional knockout systems greatly facilitated dissecting the precise mechanisms by which HDAC1,2 control genome stability in normal and cancer cells. In this perspective, I summarize the findings on the mechanistic functions of class I HDACs, specifically, HDAC1,2 in genome maintenance, unanswered questions for future investigations and views on how this knowledge could be harnessed for bettertargeted cancer therapeutics for a subset of cancers. © 2015, Taylor & Francis Group, LLC.


Stehlik J.,University of Utah
Journal of Heart and Lung Transplantation | Year: 2014

The evaluation of organ donors is of critical importance in all areas of solid organ transplantation. Donor characteristics have been shown to have robust effects on heart transplant recipient outcomes, and evaluation of the donor for suitability for heart transplantation is therefore very comprehensive. The donor evaluation process is composed of several steps, beginning with the identification of a potential organ donor and ending with the transplantation of a donor heart. The purpose of this review is to dissect the complex process of donor evaluation into its component steps and to highlight the diverse approaches used by transplant clinicians around the world to optimize outcomes at each step. We provide a summary of donor characteristics that have been associated with increased recipient mortality and discuss areas of uncertainty. Recent additions to the literature present novel insights and solutions to vexing problems in donor evaluation, such as how to make a more accurate assessment of allograft quality. Continued advancement in the evaluation of donors is essential to maintain heart transplantation as a viable therapy that provides excellent long-term survival for patients with end-stage heart failure. © 2014 International Society for Heart and Lung Transplantation. All rights reserved.


Christian J.L.,University of Utah
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2012

Morphogens are substances that establish a graded distribution and elicit distinct cellular responses in a dose-dependent manner. They function to provide individual cells within a field with positional information, which is interpreted to give rise to spatial patterns. Morphogens can consist of intracellular factors that set up a concentration gradient by diffusion in the cytoplasm. More commonly, morphogens comprise secreted proteins that form an extracellular gradient across a field of cells. Experimental studies and computational analyses have provided support for a number of diverse strategies by which extracellular morphogen gradients are formed. These include free diffusion in the extracellular space, restricted diffusion aided by interactions with heparan sulfate proteoglycans, transport on lipid-containing carriers or transport aided by soluble binding partners. More specialized modes of transport have also been postulated such as transcytosis, in which repeated rounds of secretion, endocytosis, and intracellular trafficking move morphogens through cells rather than around them, or cytonemes, which consist of filopodial extensions from signal-receiving cells that are hypothesized to reach out to morphogen-sending cells. Once the gradient has formed, cells must distinguish small differences in morphogen concentration and store this information even after the gradient has dissipated. This is often achieved by translating ligand concentration into a proportional increase in numbers of activated cell surface receptors that are internalized and continue to signal from endosomal compartments. Ultimately, this leads to activation of one or a few transcription factors that transduce this information into qualitatively distinct gene responses inside the nucleus. © 2011 Wiley Periodicals, Inc.


Sahayanathan S.,Bhabha Atomic Research Center | Godambe S.,University of Utah
Monthly Notices of the Royal Astronomical Society | Year: 2012

We model the simultaneous observations of the flat-spectrum radio quasar 3C279 at radio, optical, X-ray and very high energy (VHE) gamma-ray energies during 2006 flare using a simple one-zone leptonic model. We consider synchrotron emission due to cooling of a non-thermal electron distribution in an equipartition magnetic field and inverse Compton emission due to the scattering of synchrotron photons (SSC) and external soft photons (EC) by the same distribution of electrons. We show that the VHE gamma-ray flux cannot be explained by an SSC process thereby suggesting the EC mechanism as a plausible emission process at this energy. The EC scattering of broad-line region photons to very high energies will be in the Klein-Nishina regime predicting a steep spectrum which is contrary to the observations. However, the infrared photons from the dusty torus can be boosted to very high energies with the scattering process remaining in the Thomson regime. Though the EC process can successfully explain the observed VHE flux, it requires a magnetic field much lower than the equipartition value to reproduce the observed X-ray flux. Hence, we attribute the X-ray emission to the SSC process. We derive the physical parameters of 3C279 considering the above-mentioned emission processes. In addition, we assume the size of the emission region constrained by a variability time-scale of one day. This model can successfully reproduce the broad-band spectrum of 3C279 but predicts substantially large flux at MeV-GeV energies. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.


Contreras J.L.,University of Utah
Trends in Genetics | Year: 2015

NIH's new genomic data sharing (GDS) policy covers both human and model-organism genotypic and phenotypic data, and strives to balance rapid release of data with embargo periods to ensure that data producers have sufficient time to analyze their results. But how well does the policy achieve this balance? © 2014 Elsevier Ltd.


Frost A.,University of Utah
Current Biology | Year: 2011

Proteins involved in membrane traffic must distinguish between different classes of vesicles. New work now shows that α-synuclein and ALPS motifs represent two extreme types of amphipathic helix that are tuned to detect both the curvature of transport vesicles as well as their bulk lipid content. © 2011 Elsevier Ltd. All rights reserved.