University of Colorado Boulder
  • Boulder, CO, United States
Recent publications
The field of psychoneuroimmunology has made significant advances in understanding mechanisms underlying signaling between the immune system and central nervous system since the initial coinage of the term in 1975 and especially in the past 25 years. The current review explores the research supporting the premise that the immune system impacts behavior, including risk of developing stress-related psychiatric disorders (e.g., anxiety disorders, affective disorders, and trauma- and stressor-related disorders such as posttraumatic stress disorder). Beginning with the recent call to examination of interoception as a mental health-relevant signal, inflammation is explored as an important interoceptive signal. Inflammation is viewed through the lens of sickness behavior, before broadening to include the impact of the immune system on a collection of mental-health-related symptoms. This is explored mechanistically through the direct effects of cytokine signaling on the brain, the impact of afferent vagus nerve signaling, and through examination of the role of bone-marrow-derived monocytes in relaying peripheral immune signals to the brain. Immature bone-marrow-derived monocytes contribute to increased peripheral inflammation, but also have the capacity to traffic to brain regions relevant to stress-related psychiatric disorders. This trafficking can increase neuroinflammation causing anxiety-like defensive behavioral responses in mouse models and has been linked to symptoms of stress-related psychiatric disorders in humans. Additionally, the commensal bacteria inhabiting the gut (gut microbiota) exert a modulating effect on inflammation and behavior through several mechanisms, including signaling in the systemic circulation, shifting the body's stress dynamics, and altering inflammatory balance in the gut and the rest of the body. These mechanisms are discussed in the context of mental health conditions, including mood disorders, anxiety disorders, and trauma- and stressor-related disorders. There is a preponderance of evidence supporting the fact that peripheral immune activity and neuroinflammation impact behavior and mental health. Further research will continue to elucidate the mechanisms involved.
We present a numerical and experimental framework for the inspection of double cantilever beam composite coupons that are fabricated by bonding two composite laminates. The method is based on a mode-matching procedure in which the experimental dispersion curves of guided wave modes supported by the coupons are compared with those computed by a numerical model in which the bond strength is progressively updated until a match is achieved. Specifically, guided waves are generated in the coupons in the 0–250 kHz range by direct contact excitation with a wedge beam transducer. Their corresponding velocity field is recorded using infrared laser vibrometry. From the measured velocity arrays, the dispersion curves of several higher order modes are extracted and subsequently used to match a semi-analytical finite element model of the coupons. The updating procedure is based on two steps. In the first step, the dispersion data of a coupon with a known pristine bond are used to determine the orthotropic elastic coefficients of the composite laminae. In the second step, these coefficients are fixed and only the bond equivalent Young’s modulus is updated by using the experimental dispersion curves. Analyses performed on coupons with three different level of seeded contamination indicate that our proposed method can quantify their reduction with good accuracy, which makes the method suitable for the efficient non-destructive inspection of structural components.
In this conceptual paper, we describe the approach in storylines that builds on principles of project-based learning and focuses on supports for making science learning coherent from the students’ perspective. In storylines, students see their science work as addressing questions and problems their class has identified. We present design principles that guide the teaching and enactment of storyline units and explore the connections of these principles to ideas of project-based science. We illustrate how these design strategies are reflected in a high school biology unit co-developed by teachers and researchers. We present student artifacts that document the agency students take on in this work. We then summarize results from earlier studies examining students’ learning and perceptions of coherence of their learning experiences.
Aim To investigate mask use and the difficulties it may pose during communication in healthcare settings. Methods A survey utilizing a series of Likert scales was administered. Mask use challenges between clinicians and their patients were examined in the domains of communication, listening effort, cognition, and rehabilitation. Results Across 243 participants, mask use significantly increased listening effort, with hearing loss having an additive effect on listening effort. Listening effort was also significantly associated with more trouble understanding conversation, decreased interest in conversation, more difficulty connecting with patients, changes in cognition for both providers and patients, and changes in the clinical efficiency of providers. Hearing loss had an additive effect for trouble understanding conversations and changes in clinical efficiency. Conclusion These results provide information about the clinical strain introduced from mask use in healthcare settings. Overall, results show that in healthcare settings there is increased cognitive load and listening effort for both patients and providers, as well as changes in clinical efficiency for providers when utilizing masks. These effects are often greater with hearing loss. Results showed that patients reported written and visual instructions would be most beneficial to include in appointments among the other rehabilitative strategies which are discussed.
Background: Dental personnel are at risk of developing occupational contact dermatitis. Objectives: The aims of the study were to determine prevalence of occupational contact dermatitis in dental personnel referred for patch testing and to characterize relevant allergens and sources. Methods: The study used a retrospective, cross-sectional analysis of the North American Contact Dermatitis Group (NACDG) data, 2001-2018. Results: Of 41,109 patients, 585 (1.4%) were dental personnel. Dental personnel were significantly more likely than nondental personnel to be female (75.7% vs 67.4%, P < 0.0001), have occupationally related dermatitis (35.7% vs 11.5%, P < 0.0001), and/or have primary hand involvement (48.6% vs 22.5%, P < 0.0001). More than one quarter of dental personnel (62/585, 27.7%) had 1 or more occupationally related allergic patch test reaction(s). There were 249 occupationally related reactions to NACDG screening allergens, most commonly glutaraldehyde (18.1%), thiuram mix (16.1%), and carba mix (14.1%). The most common sources of NACDG screening allergens were gloves (30.7%), dental materials (26.6%), and sterilizing solutions (13.1%). Seventy-three dental personnel (12.5%) had 1 or more positive patch test reactions to occupationally related allergen(s)/substances not on the screening series. Occupationally related irritant contact dermatitis was identified in 22.2% (n = 130) of dental personnel, most commonly to nonskin soaps/detergents/disinfectants (32.0%). Conclusions: Occupational contact dermatitis is common in dental personnel referred for patch testing. Comprehensive testing beyond screening series is important in these patients.
Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.
Background Anthocyanins are major pigments contributing to flower coloration and as such knowledge of molecular architecture underlying the anthocyanin biosynthetic pathway (ABP) is key to understanding flower color diversification. To identify ABP structural genes and associated regulatory networks, we sequenced 16 transcriptomes generated from 10 species of Ruellia and then conducted co-expression analyses among resulting data. Results Complete coding sequences for 12 candidate structural loci representing eight genes plus nine candidate regulatory loci were assembled. Analysis of non-synonymous/synonymous (dn/ds) mutation rates indicated all identified loci are under purifying selection, suggesting overall selection to prevent the accumulation of deleterious mutations. Additionally, upstream enzymes have lower rates of molecular evolution compared to downstream enzymes. However, site-specific tests of selection yielded evidence for positive selection at several sites, including four in F3'H2 and five in DFR3 , and these sites are located in protein binding regions. A species-level phylogenetic tree constructed using a newly implemented hybrid transcriptome–RADseq approach implicates several flower color transitions among the 10 species. We found evidence of both regulatory and structural mutations to F3′5'H in helping to explain the evolution of red flowers from purple-flowered ancestors. Conclusions Sequence comparisons and co-expression analyses of ABP loci revealed that mutations in regulatory loci are likely to play a greater role in flower color transitions in Ruellia compared to mutations in underlying structural genes.
Surgical patients with coronavirus disease 2019 (COVID-19) are vulnerable to increased perioperative complications and postoperative mortality, independent of the risk for contracting COVID-19 pneumonia after endotracheal intubation for general anesthesia. The presumed root cause of postoperative infections, microvascular soft tissue injuries and thromboembolic complications is largely attributed to the profound immune dysfunction induced by COVID-19 as a result of complement activation and the “cytokine storm”. The empirical therapy with anti-inflammatory agents has been shown to attenuate some of the adverse effects of systemic hyperinflammation in COVID-19 patients. In addition, the proactive concept of “immunonutrition” may represent a new promising avenue for mitigating the complex immune dysregulation in COVID-19 and thereby reduce the rates of surgical complications and postoperative mortality. This letter provides a narrative summary of the current state-of-the-art in the field of immunonutrition as it pertains to surgical patient safety in COVID-19 patients.
Background: The 2016 U.S. Centers for Disease Control Opioid Prescribing Guideline (CDC Guideline) is currently being revised amid concern that it may be harmful to people with chronic pain on long-term opioid therapy (CP-LTOT). However, a methodology to faithfully implement the CDC guideline, measure prescriber adherence, and systematically test its effect on patient and public health outcomes is lacking. We developed and tested a CDC Guideline implementation strategy (termed TOWER), focusing on an outpatient HIV-focused primary care setting. Methods: TOWER was developed in a stakeholder-engaged, multi-step iterative process within an Information, Motivation and Behavioral Skills (IMB) framework of behavior change. TOWER consists of: 1) a patient-facing opioid management app (OM-App); 2) a progress note template (OM-Note) to guide the office visit; and 3) a primary care provider (PCP) training. TOWER was evaluated in a 9-month, randomized-controlled trial of HIV-PCPs (N = 11) and their patients with HIV and CP-LTOT (N = 40). The primary outcome was CDC Guideline adherence based on electronic health record (EHR) documentation and measured by the validated Safer Opioid Prescribing Evaluation Tool (SOPET). Qualitative data including one-on-one PCP interviews were collected. We also piloted patient-reported outcome measures (PROMs) reflective of domains identified as important by stakeholders (pain intensity and function; mood; substance use; medication use and adherence; relationship with provider; stigma and discrimination). Results: PCPs randomized to TOWER were 48% more CDC Guideline adherent (p < 0.0001) with significant improvements in use of: non-pharmacologic treatments, functional treatment goals, opioid agreements, prescription drug monitoring programs (PDMPs), opioid benefit/harm assessment, and naloxone prescribing. Qualitative data demonstrated high levels of confidence in conducting these care processes among intervention providers, and that OM-Note supported these efforts while experience with OM-App was mixed. There were no intervention-associated safety concerns (defined as worsening of any of the PROMs). Conclusions: CDC-guideline adherence can be promoted and measured, and is not associated with worsening of outcomes for people with HIV receiving LTOT for CP. Future work would be needed to document scalability of these results and to determine whether CDC-guideline adherence results in a positive effect on public health. Trial registration . Registration date: 9/13/2018.
In humans, an adaptable internal biological system generates circadian rhythms that maintain synchronicity of behavior and physiology with the changing demands of the 24-h environment. Development of the circadian system begins in utero and continues throughout the first few years of life. Maturation of the clock can be measured through sleep/wake patterns and hormone secretion. Circadian rhythms, by definition, can persist in the absence of environmental input; however, their ability to adjust to external time cues is vital for adaptation and entrainment to the environment. The significance of these external factors that influence the emergence of a stable circadian clock in the first years of life remain poorly understood. Infants raised in our post-modern world face adverse external circadian signals, such as artificial light and mistimed hormonal cues via breast milk, which may increase interference with the physiological mechanisms that promote circadian synchronization. This review describes the very early developmental stages of the clock and common circadian misalignment scenarios that make the developing circadian system more susceptible to conflicting time cues and temporal disorder between the maternal, fetal, infant, and peripheral clocks.
Background Regulator of calcineurin 1 ( RCAN1 ) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer’s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. Methods The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3–6 months old) and aged (9–14 months old) mice of both sexes. Results We found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ ( Dp16 ) mouse model for DS, which expresses three copies of Rcan1 , we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN. Conclusions Collectively, this study’s findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging.
Many concepts are defined by their relationships to one another. However, instructors might teach these concepts individually, neglecting their interconnections. For instance, students learning about statistical power might learn how to define alpha and beta, but not how they are related. We report two experiments that examine whether there is a benefit to training subjects on relations among concepts. In Experiment 1, all subjects studied material on statistical hypothesis testing, half were subsequently quizzed on relationships among these concepts, and the other half were quizzed on their individual definitions; quizzing was used to highlight the information that was being trained in each condition (i.e., relations or definitions). Experiment 2 also included a mixed training condition that quizzed both relations and definitions, and a control condition that only included study. Subjects were then tested on both types of questions and on three conceptually related question types. In Experiment 1, subjects trained on relations performed numerically better on relational test questions than subjects trained on definitions (nonsignificant trend), whereas definitional test questions showed the reverse pattern; no performance differences were found between the groups on the other question types. In Experiment 2, relational training benefitted performance on relational test questions and on some question types that were not quizzed, whereas definitional training only benefited performance on test questions on the trained definitions. In contrast, mixed training did not aid learning above and beyond studying. Relational training thus seems to facilitate transfer of learning, whereas definitional training seems to produce training specificity effects.
Objective Microbial dysbiosis, a shift from commensal to pathogenic microbiota, is often associated with mental health and the gut–brain axis, where dysbiosis in the gut may be linked to dysfunction in the brain. Many studies focus on dysbiosis induced by clinical events or traumatic incidents; however, many professions in austere or demanding environments may encounter continuously compounded stressors. This study seeks to explore the relationship between microbial populations and stress, both perceived and biochemical. Results Eight individuals enrolled in the study to provide a longitudinal assessment of the impact of stress on gut health, with four individuals providing enough samples for analysis. Eleven core microbial genera were identified, although the relative abundance of these genera and other members of the microbial population shifted over time. Although our results indicate a potential relationship between perceived stress and microbial composition of the gut, no association with biochemical stress was observed. Increases in perceived stress seem to elucidate a change in potentially beneficial Bacteroides , with a loss in Firmicutes phyla. This shift occurred in multiple individuals, whereas using cortisol as a stress biomarker showed contradictory responses. These preliminary data provide a potential mechanism for gut monitoring, while identifying targets for downstream modulation.
Let G be a graph with vertex set V(G), and let d(x,y) denote the length of a shortest path between nodes x and y in G. For a positive integer k and for distinct x,y∈V(G), let dk(x,y)=min{d(x,y),k+1} and Rk{x,y}={z∈V(G):dk(x,z)≠dk(y,z)}. A subset S⊆V(G) is a k-truncated resolving set of G if |S∩Rk{x,y}|≥1 for any pair of distinct x,y∈V(G). The k-truncated metric dimension, dimk(G), of G is the minimum cardinality over all k-truncated resolving sets of G, and the usual metric dimension is recovered when k+1 is at least the diameter of G. We obtain some general bounds for k-truncated metric dimension. For all k≥1, we characterize connected graphs G of order n with dimk(G)=n−2 and dimk(G)=n−1. For all j,k≥1, we find the maximum possible order, degree, clique number, and chromatic number of any graph G with dimk(G)=j. We determine dimk(G) when G is a cycle or a path. We also examine the effect of vertex or edge deletion on the truncated metric dimension of graphs, and study various problems related to the truncated metric dimension of trees.
Human papillomavirus (HPV) infection is a causative agent of multiple human cancers, including cervical and head and neck cancers. In these HPV-positive tumors, somatic mutations are caused by aberrant activation of DNA mutators such as members of the apolipoprotein B messenger RNA–editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytidine deaminases. APOBEC3 proteins are most notable for their restriction of various viruses, including anti-HPV activity. However, the potential role of APOBEC3 proteins in HPV-induced cancer progression has recently garnered significant attention. Ongoing research stems from the observations that elevated APOBEC3 expression is driven by HPV oncogene expression and that APOBEC3 activity is likely a significant contributor to somatic mutagenesis in HPV-positive cancers. This review focuses on recent advances in the study of APOBEC3 proteins and their roles in HPV infection and HPV-driven oncogenesis. Further, we discuss critical gaps and unanswered questions in our understanding of APOBEC3 in virus-associated cancers. Expected final online publication date for the Annual Review of Virology, Volume 9 is September 2022. Please see for revised estimates.
The objective of this paper is to provide an introduction to high-quality, practical, and evidence-based instructional resources from medical educators that can be adapted and adopted by accounting educators. The American Accounting Association (AAA) Pathways Commission Final Report set a goal of accounting becoming a learned profession by 2036. An AAA Presidential Scholar has advised that the achievement of this goal will require collaboration with other academic areas inside and beyond the business school. Responding to this call, this paper identifies a subset of Association for Medical Education in Europe (AMEE) Medical Education Guides that are relevant to accounting educators interested in problem-based learning (PBL), team-based learning (TBL), peer assisted learning (PAL) and reflection. Other opportunities for application of the medical resources to faculty responsibilities in teaching, research and service are shared to encourage accounting educators to learn from a well-established learned profession.
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Philip Graves
  • Department of Economics
Mihaly Horanyi
  • Department of Physics
Zoltan Sternovsky
  • Laboratory for Atmospheric and Space Physics (LASP)
Dragan Maksimovic
  • Department of Electrical, Computer, and Energy Engineering (ECEE)
Mingwei Min
  • Department of Chemistry and Biochemistry
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