• The Hagiography of a Secular Saint: Alexander von Humboldt and the Scientism of the German Democratic Republic

      Howell, James F.; Univ Arizona (WILEY, 2018-02)
      Throughout its existence, the German Democratic Republic attempted to supplant religious authority and beliefs by promoting a wissenschaftliche Weltanschauung that served as a secular alternative for metaphysical frameworks of understanding and cultural orientation. An integral part of this program of substitution was the Marxist‐Leninist rehabilitation of certain members of the German canon who best embodied the socialist and scientistic potential of the German cultural tradition. As a figure who stood at the forefront of this group, Alexander von Humboldt was reimagined by the East German cultural apparatus as a “spontaneous materialist,” an educator of the masses who fought on the side of the oppressed worldwide. This analysis elucidates the ways in which the East German cultural apparatus appropriated and reconfigured Humboldt to fit its needs, as well as how, more generally, the SED designed and implemented a scientistic worldview that continues to affect and shape culture in eastern Germany today.
    • Predictors of sleepiness in obstructive sleep apnoea at baseline and after 6 months of continuous positive airway pressure therapy

      Budhiraja, Rohit; Kushida, Clete A.; Nichols, Deborah A.; Walsh, James K.; Simon, Richard D.; Gottlieb, Daniel J.; Quan, Stuart F.; Univ Arizona, Arizona Resp Ctr
      We evaluated factors associated with subjective and objective sleepiness at baseline and after 6 months of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA). We analysed data from the Apnoea Positive Pressure Long-term Efficacy Study (APPLES), a prospective 6-month multicentre randomised controlled trial with 1105 subjects with OSA, 558 of who were randomised to active CPAP. Epworth sleepiness scale (ESS) scores and the mean sleep latency (MSL) on the maintenance of wakefulness test at baseline and after 6 months of CPAP therapy were recorded. Excessive sleepiness (ESS score > 10) was present in 543 (49.1%) participants. Younger age, presence of depression and higher apnoea-hypopnoea index were all associated with higher ESS scores and lower MSL. Randomisation to the CPAP group was associated with lower odds of sleepiness at 6 months. The prevalence of sleepiness was significantly lower in those using CPAP > 4 h center dot night(-1) versus using CPAP. <= 4 h center dot night(-1). Among those with good CPAP adherence, those with ESS > 10 at baseline had significantly higher odds (OR 8.2, p<0.001) of persistent subjective sleepiness. Lower average nightly CPAP use and presence of sleepiness at baseline were independently associated with excessive subjective and objective sleepiness after 6 months of CPAP therapy.
    • Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder

      Weihs, Karen L.; Murphy, William; Abbas, Richat; Chiles, Deborah; England, Richard D.; Ramaker, Sara; Wajsbrot, Dalia B.; Univ Arizona, Dept Psychiat (MARY ANN LIEBERT, INC, 2018-02)
      Objectives: To evaluate the short-term efficacy and safety of desvenlafaxine (25-50mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). Methods: Outpatient children (7-11 years) and adolescents (12-17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale-Revised (CDRS-R) total scores >40 were randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50mg/d based on baseline weight), or fluoxetine (20mg/d). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy endpoints included week 8 Clinical Global Impressions-Severity, Clinical Global Impressions-Improvement (CGI-I), and response (CGI-I 2). Safety assessments included adverse events, physical and vital sign measurements, laboratory evaluations, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Results: The safety population included 339 patients (children, n=130; adolescents, n=209). The primary endpoint, change from baseline in CDRS-R total score at week 8, did not statistically separate from placebo, for either desvenlafaxine (adjusted mean [standard error] change, -22.6 [1.17]) or fluoxetine (-24.8 [1.17]; placebo, -23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for fluoxetine (78.2%; p=0.017) than for placebo (62.6%); desvenlafaxine (68.7%) did not differ from placebo. Other secondary outcomes were consistent with those obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine, 64.3%). Conclusion: Desvenlafaxine did not demonstrate efficacy for treating MDD in children and adolescents in this trial. Because neither desvenlafaxine nor the reference medication, fluoxetine, demonstrated a statistically significant difference from placebo on the primary endpoint, this was considered a failed trial and no efficacy conclusions can be drawn. Desvenlafaxine 25-50mg/d was generally safe and well tolerated in children and adolescents in this study.
    • Differential release of dopamine in the nucleus accumbens evoked by low-versus high-frequency medial prefrontal cortex stimulation

      Hill, Daniel F.; Parent, Kate L.; Atcherley, Christopher W.; Cowen, Stephen L.; Heien, Michael L.; Univ Arizona, Dept Physiol; Univ Arizona, Dept Chem & Biochem; Univ Arizona, Evelyn F McKnight Brian Inst
      The medial prefrontal cortex (mPFC) coordinates goal-directed behaviors, which may be mediated through mPFC regulation of dopamine release in the nucleus accumbens (NAc). Furthermore, frequency-specific oscillatory activity between the frontal cortex and downstream structures may facilitate interregion communication. Although high-frequency (e.g., 60 Hz) mPFC stimulation is known to increase basal dopamine levels in the NAc, little is known about how phasic dopamine release is affected by mPFC stimulation. Understanding the frequency-specific control of phasic dopamine release by mPFC stimulation could elucidate mechanisms by which the mPFC modulates other regions. It could also inform optimization of deep brain stimulation for treatment of neurological disorders. Objective: The goal of this work was to characterize the frequency response of NAc dopamine release resultant from mPFC stimulation. We hypothesized that the magnitude of dopamine release in the NAc would increase with increasing stimulation frequency. Methods: Electrical stimulation of the mPFC of anesthetized rats was delivered at 4-60 Hz and at varying durations while measuring NAc dopamine release with fast-scan cyclic voltammetry. Results: mPFC stimulation resulted in phasic dopamine release in the NAc. Furthermore, 20 Hz stimulation evoked the largest peak response for stimulation intervals > 5 s when compared to higher or lower frequencies. Conclusions: Activation of the mPFC drives dopamine release in the NAc in a complex frequency- and duration-dependent manner. This has implications for the use of deep brain stimulation treatment of disorders marked by dopaminergic dysregulation, and suggest that mPFC may exert more specialized control over neuromodulator release than previously understood. (C) 2017 Published by Elsevier Inc.
    • A gender- and culturally-sensitive weight loss intervention for Hispanic males: The ANIMO randomized controlled trial pilot study protocol and recruitment methods

      Garcia, David O.; Valdez, Luis A.; Bell, Melanie L.; Humphrey, Kyle; Hingle, Melanie; McEwen, Marylyn; Hooker, Steven P.; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Dept Hlth Promot Sci; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Dept Epidemiol & Biostat; Univ Arizona, Coll Agr & Life Sci; Univ Arizona, Coll Nursing (ELSEVIER INC, 2018-03)
      Hispanic men have the highest rates of overweight and obesity when compared to men of other racial/ethnic groups, placing them at increased risk for obesity-related disease. Yet, Hispanic men are grossly under-represented in weight loss research. Tailored intervention strategies to improve obesity treatment programs for this vulnerable racial/ethnic subgroup are needed. This manuscript describes recruitment strategies, methodology, and participant characteristics of the ANIMO study, a 24-week randomized controlled pilot trial testing the effects of a gender-and culturally-sensitive weight loss intervention (GCSWLI) on body weight in Hispanic men compared to a wait-list control condition. The ANIMO study included two phases. The first phase was a 12-week GCSWLI. Participants attended weekly in-person individual sessions guided by a trained bilingual Hispanic male lifestyle coach, were prescribed a daily reduced calorie goal, and 225 min of moderate-intensity physical activity per week. In the second phase, GCSWLI participants received bi-weekly phone calls across a 12-week follow-up. Wait-list control (WLC) participants from phase 1 received the GCSWLI plus mobile health technology support. Recruitment strategies included face-to-face efforts at a swap meet (outdoor marketplace), family/friend referrals, printed advertisements and social media. Recruitment, screening, and participant enrollment occurred over three months. Overall, 143 men expressed interest in participation. Of these, 115 were screened and 78% (n=90) were eligible to participate; 45% of enrolled participants (n=52) completed baseline assessments and 43% (n=50) were randomized (mean age of 43.3 +/- 11.4 years; BMI: 34.1 +/- 5.3 kg/m(2); 58% Spanish monolingual). Parameter estimates from ANIMO will support future adequately powered trials for this health disparate population.
    • Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia

      Godfrey, Lisa; Iannitelli, Antonio; Garrett, Natalie L.; Moger, Julian; Imbert, Ian; King, Tamara; Porreca, Frank; Soundararajan, Ramesh; Lalatsa, Aikaterini; Schätzlein, Andreas G.; Uchegbu, Ijeoma F.; Univ Arizona, Coll Med, Dept Pharmacol (ELSEVIER SCIENCE BV, 2017-11-27)
      The delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine(5)-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on going pain whereas animals dosed intranasally with LENK alone were unresponsive. Animals did not develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was active in morphine tolerant animals. A microparticulate formulation of clustered nanoparticles was prepared to satisfy regulatory requirements for nasal dosage forms and the polymer nanoparticles alone were found to be biocompatible, via the nasal route, on chronic dosing.
    • Crack the state of silence: Tune the depth of cellular quiescence for cancer therapy

      Fujimaki, Kotaro; Yao, Guang; Univ Arizona, Dept Mol & Cellular Biol; Univ Arizona, Arizona Canc Ctr (TAYLOR & FRANCIS INC, 2017-12)
      The regulation cif cellular quiescence underlies numerous physiopathological phenomena. We recently found that quiescence depth can be tuned as to adjust a dimmer switch, by altering the expression of genes in the Retinoblastoma (Rb)-E2f pathway. Reducing quiescence depth may wake dormant cancer cells and make them susceptible to treatment.
    • PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction

      Guzman-Villanueva, Diana; Migrino, Raymond Q.; Truran, Seth; Karamanova, Nina; Franco, Daniel A.; Burciu, Camelia; Senapati, Subhadip; Nedelkov, Dobrin; Hari, Parameswaran; Weissig, Volkmar; Univ Arizona, Coll Med (TAYLOR & FRANCIS LTD, 2018-02)
      Light chain (AL) amyloidosis is a disease associated with significant morbidity and mortality arising from multi-organ injury induced by amyloidogenic light chain proteins (LC). There is no available treatment to reverse the toxicity of LC. We previously showed that chaperone glycoprotein clusterin (CLU) and nanoliposomes (NL), separately, restore human microvascular endothelial function impaired by LC. In this work, we aim to prepare PEGylated-nanoliposomal clusterin (NL-CLU) formulations that could allow combined benefit against LC while potentially enabling efficient delivery to microvascular tissue, and test efficacy on human arteriole endothelial function. NL-CLU was prepared by a conjugation reaction between the carboxylated surface of NL and the primary amines of the CLU protein. NL were made of phosphatidylcholine (PC), cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (DSPE-PEG 2000 carboxylic acid) at 70:25:5mol%. The protective effect of NL-CLU was tested by measuring the dilation response to acetylcholine and papaverine in human adipose arterioles exposed to LC. LC treatment significantly reduced the dilation response to acetylcholine and papaverine; co-treatment of LC with PEGylated-nanoliposomal CLU or free CLU restored the dilator response. NL-CLU is a feasible and promising approach to reverse LC-induced endothelial damage.
    • Natural language indicators of differential gene regulation in the human immune system

      Mehl, Matthias R.; Raison, Charles L.; Pace, Thaddeus W. W.; Arevalo, Jesusa M. G.; Cole, Steve W.; Univ Arizona, Dept Psychol (NATL ACAD SCIENCES, 2017-11-21)
      Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS mechanisms involved remain obscure, in part because CTRA gene-expression profiles often track external social-environmental variables more closely than they do self-reported internal affective states such as stress, depression, or anxiety. This study examined the possibility that variations in patterns of natural language use might provide more sensitive indicators of the automatic threat- detection and -response systems that proximally regulate autonomic induction of the CTRA. In 22,627 audio samples of natural speech sampled from the daily interactions of 143 healthy adults, both total language output and patterns of function-word use covaried with CTRA gene expression. These language features predicted CTRA gene expression substantially better than did conventional self-report measures of stress, depression, and anxiety and did so independently of demographic and behavioral factors (age, sex, race, smoking, body mass index) and leukocyte subset distributions. This predictive relationship held when language and gene expression were sampled more than a week apart, suggesting that associations reflect stable individual differences or chronic life circumstances. Given the observed relationship between personal expression and gene expression, patterns of natural language use may provide a useful behavioral indicator of nonconsciously evaluated well-being (implicit safety vs. threat) that is distinct from conscious affective experience and more closely tracks the neurobiological processes involved in peripheral gene regulation.
    • BAYSPLINE: A New Calibration for the Alkenone Paleothermometer

      Tierney, Jessica E.; Tingley, Martin P.; Univ Arizona, Dept Geosci (AMER GEOPHYSICAL UNION, 2018-03)
      The alkenone-based U-37(K') proxy is a cornerstone of paleoclimatology, providing insight into the temperature history of the Earth's surface ocean. Although the relationship between U-37(K') and sea surface temperatures (SSTs) is robust and well supported by experimental data, there remain outstanding issues regarding the seasonality of production of alkenones and the response of U-37(K') at very warm and cold SSTs. Using a data set of over 1,300 core-top U-37(K') measurements, we find compelling evidence of seasonal production in the North Atlantic, North Pacific, and Mediterranean Oceans. We also find significant attenuation of the U-37(K') response to SST at warm temperatures (> 24 degrees C), with the slope reduced by nearly 50% as U-37(K') approaches unity. To account for these observations in a calibration, we develop a new Bayesian B-spline regression model, BAYSPLINE, for the U-37(K') paleothermometer. BAYSPLINE produces similar estimates as previous calibrations below similar to 24 degrees, but above this point it predicts larger SST changes, in accordance with the attenuation of the U-37(K') response. Example applications of BAYSPLINE demonstrate that its treatment of seasonality and slope attenuation improves paleoclimatic interpretations, with important consequences for the inference of SSTs in the tropical oceans. BAYSPLINE facilitates a probabilistic approach to paleoclimate, building upon growing efforts to develop more formalized statistical frameworks for paleoceanographic reconstruction. Plain Language Summary "Alkenones" are lipids (fats) made by marine phytoplankton. The plankton alter the degree of unsaturation in these lipids in response to sea surface temperature (SST), producing more unsaturated compounds in colder water. These lipids are well preserved in marine sediments, such that paleoclimatologists can measure the unsaturation and determine what SSTs were in the past. In this manuscript, we review the calibration of this powerful "paleothermometer" and propose a new model that uses spline fits and Bayesian regression. We find that the new model improves our ability to estimate past SSTs, especially in the tropical oceans.
    • A Reduced-Order Successive Linear Estimator for Geostatistical Inversion and its Application in Hydraulic Tomography

      Zha, Yuanyuan; Yeh, Tian-Chyi J.; Illman, Walter A.; Zeng, Wenzhi; Zhang, Yonggen; Sun, Fangqiang; Shi, Liangsheng; Univ Arizona, Dept Hydrol & Atmospher Sci (AMER GEOPHYSICAL UNION, 2018-03)
      Hydraulic tomography (HT) is a recently developed technology for characterizing high-resolution, site-specific heterogeneity using hydraulic data (n(d)) from a series of cross-hole pumping tests. To properly account for the subsurface heterogeneity and to flexibly incorporate additional information, geostatistical inverse models, which permit a large number of spatially correlated unknowns (n(y)), are frequently used to interpret the collected data. However, the memory storage requirements for the covariance of the unknowns (n(y) x n(y)) in these models are prodigious for large-scale 3-D problems. Moreover, the sensitivity evaluation is often computationally intensive using traditional difference method (n(y) forward runs). Although employment of the adjoint method can reduce the cost to n(d) forward runs, the adjoint model requires intrusive coding effort. In order to resolve these issues, this paper presents a Reduced-Order Successive Linear Estimator (ROSLE) for analyzing HT data. This new estimator approximates the covariance of the unknowns using Karhunen-Loeve Expansion (KLE) truncated to n(kl) order, and it calculates the directional sensitivities (in the directions of n(kl) eigenvectors) to form the covariance and cross-covariance used in the Successive Linear Estimator (SLE). In addition, the covariance of unknowns is updated every iteration by updating the eigenvalues and eigenfunctions. The computational advantages of the proposed algorithm are demonstrated through numerical experiments and a 3-D transient HT analysis of data from a highly heterogeneous field site.
    • Implementing Dynamic Root Optimization in Noah-MP for Simulating Phreatophytic Root Water Uptake

      Wang, Ping; Niu, Guo-Yue; Fang, Yuan-Hao; Wu, Run-Jian Run-Jian; Yu, Jing-Jie; Yuan, Guo-Fu; Pozdniakov, Sergey P.; Scott, Russell L.; Univ Arizona, Dept Hydrol & Atmospher Sci; Univ Arizona, Biosphere 2 (AMER GEOPHYSICAL UNION, 2018-03)
      Widely distributed in arid and semiarid regions, phreatophytic roots extend into the saturated zone and extract water directly from groundwater. In this paper, we implemented a vegetation optimality model of root dynamics (VOM-ROOT) in the Noah land surface model with multiparameterization options (Noah-MP LSM) to model the extraction of groundwater through phreatophytic roots at a riparian site with a hyperarid climate (with precipitation of 35 mm/yr) in northwestern China. VOM-ROOT numerically describes the natural optimization of the root profile in response to changes in subsurface water conditions. The coupled Noah-MP/VOM-ROOT model substantially improves the simulation of surface energy and water fluxes, particularly during the growing season, compared to the prescribed static root profile in the default Noah-MP. In the coupled model, more roots are required to grow into the saturated zone to meet transpiration demand when the groundwater level declines over the growing season. The modeling results indicate that at the study site, the modeled annual transpiration is 472 mm, accounting for 92.3% of the total evapotranspiration. Direct root water uptake from the capillary fringe and groundwater, which is supplied by lateral groundwater flow, accounts for approximately 84% of the total transpiration. This study demonstrates the importance of implementing a dynamic root scheme in a land surface model for adequately simulating phreatophytic root water uptake and the associated latent heat flux.
    • Reconnecting Stochastic Methods With Hydrogeological Applications: A Utilitarian Uncertainty Analysis and Risk Assessment Approach for the Design of Optimal Monitoring Networks

      Bode, Felix; Ferre, Ty; Zigelli, Niklas; Emmert, Martin; Nowak, Wolfgang; Univ Arizona, Dept Hydrol & Atmospher Sci (AMER GEOPHYSICAL UNION, 2018-03)
      Collaboration between academics and practitioners promotes knowledge transfer between research and industry, with both sides benefiting greatly. However, academic approaches are often not feasible given real-world limits on time, cost and data availability, especially for risk and uncertainty analyses. Although the need for uncertainty quantification and risk assessment are clear, there are few published studies examining how scientific methods can be used in practice. In this work, we introduce possible strategies for transferring and communicating academic approaches to real-world applications, countering the current disconnect between increasingly sophisticated academic methods and methods that work and are accepted in practice. We analyze a collaboration between academics and water suppliers in Germany who wanted to design optimal groundwater monitoring networks for drinking-water well catchments. Our key conclusions are: to prefer multiobjective over single-objective optimization; to replace Monte-Carlo analyses by scenario methods; and to replace data-hungry quantitative risk assessment by easy-to-communicate qualitative methods. For improved communication, it is critical to set up common glossaries of terms to avoid misunderstandings, use striking visualization to communicate key concepts, and jointly and continually revisit the project objectives. Ultimately, these approaches and recommendations are simple and utilitarian enough to be transferred directly to other practical water resource related problems.
    • Recurrent inhibition of mitochondrial complex III induces chronic pulmonary vasoconstriction and glycolytic switch in the rat lung

      Rafikova, Olga; Srivastava, Anup; Desai, Ankit A.; Rafikov, Ruslan; Tofovic, Stevan P.; Univ Arizona, Dept Med, Div Endocrinol; Univ Arizona, Dept Med (BIOMED CENTRAL LTD, 2018-04-23)
      Background: Pulmonary arterial hypertension (PAH) is a fatal disease; however, the mechanisms directly involved in triggering and the progression of PAH are not clear. Based on previous studies that demonstrated a possible role of mitochondrial dysfunction in the pathogenesis of PAH, we investigated the effects of chronic inhibition of mitochondrial function in vivo in healthy rodents. Methods: Right ventricle systolic pressure (RVSP) was measured in female rats at baseline and up to 24 days after inhibition of mitochondrial respiratory Complex III, induced by Antimycin A (AA, 035 mg/kg, given three times starting at baseline and then days 3 and 6 as a bolus injection into the right atrial chamber). Results: Rodents exposed to AA demonstrated sustained increases in RVSP from days 6 through 24. AA-exposed rodents also possessed a progressive increase in RV end-diastolic pressure but not RV hypertrophy, which may be attributed to either early stages of PAH development or to reduced RV contractility due to inhibition of myocardial respiration. Protein nitration levels in plasma were positively correlated with PAH development in AA-treated rats. This finding was strongly supported by results obtained from PAH humans where plasma protein nitration levels were correlated with markers of PAH severity in female but not male PAH patients. Based on previously reported associations between increased nitric oxide production levels with female gender, we speculate that in females with PAH mitochondrial dysfunction may represent a more deleterious form, in part, due to an increased nitrosative stress development. Indeed, the histological analysis of AA treated rats revealed a strong perivascular edema, a marker of pulmonary endothelial damage. Finally, AA treatment was accompanied by a severe metabolic shift toward glycolysis, a hallmark of PAH pathology. Conclusions: Chronic mitochondrial dysfunction induces the combination of vascular damage and metabolic reprogramming that may be responsible for PAH development. This mechanism may be especially important in females, perhaps due to an increased NO production and nitrosative stress development.
    • Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects

      Lee, Alison G.; Le Grand, Blake; Hsu, Hsiao-Hsien Leon; Chiu, Yueh-Hsiu Mathilda; Brennan, Kasey J.; Bose, Sonali; Rosa, Maria José; Brunst, Kelly J.; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Morgan, Wayne; Coull, Brent A.; Wright, Robert O.; Baccarelli, Andrea A.; Wright, Rosalind J.; Univ Arizona, Dept Pediat (BIOMED CENTRAL LTD, 2018-04-27)
      Background: In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 mu m (PM2.5) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylation. Methods: We prospectively examined associations among prenatal PM2.5 exposure and child lung function and GSTP1 methylation in an urban pregnancy cohort study. We employed a validated satellite-based spatiotemporally resolved prediction model to estimate daily prenatal PM2.5 exposure over gestation. We used Baysian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM2.5 exposure on child lung function and nasal epithelia GSTP1 methylation at age 7 years, and to examine effect modification by child sex. Results: BDLIMs identified a sensitive window for prenatal PM2.5 exposure at 35-40 weeks gestation [cumulative effect estimate (CEE) = -0.10, 95% CI = -0.19 to -0.01, per mu g/m(3) increase in PM2.5] and at 36-40 weeks (CEE = -0. 12, 95% CI = -0.20 to -0.01) on FEV1 and FVC, respectively, in boys. BDLIMs also identified a sensitive window of exposure at 37-40 weeks gestation between higher prenatal PM2.5 exposure and increased GSTP1 percent methylation. The association between higher GSTP1 percent methylation and decreased FEV1 was borderline significant in the sample as a whole (ss = -0.37, SE = 0.20, p = 0.06) and in boys in stratified analyses (ss = -0.56, SE = 0.29, p = 0.05). Conclusions: Prenatal PM2.5 exposure in late pregnancy was associated with impaired early childhood lung function and hypermethylation of GSTPI in DNA isolated from nasal epithelial cells. There was a trend towards higher GSTP1 percent methylation being associated with reduced FEV1. All findings were most evident among boys.
    • The impact of attachment distress on affect-centered mentalization: An experimental study in psychosomatic patients and healthy adults

      Herrmann, Anna S.; Beutel, Manfred E.; Gerzymisch, Katharina; Lane, Richard D.; Pastore-Molitor, Janine; Wiltink, Joerg; Zwerenz, Ruediger; Banerjeet, Mita; Subic-Wrana, Claudia; Univ Arizona, Coll Med, Dept Psychiat (PUBLIC LIBRARY SCIENCE, 2018-04-19)
      Introduction We investigated the impact of attachment distress on affect-centered mentalization in a clinical and a non-clinical sample, comparing mentalization in a baseline condition to mentalization under a condition of attachment distress. Methods The sample consisted of 127 adults who underwent inpatient psychosomatic treatment, and 34 mentally healthy adults. Affect-centered mentalization was assessed by analyzing participants' narratives on interpersonal situations in a baseline condition with the Levels of Emotional Awareness Scale (LEAS), and an experimental condition inducing attachment distress with the Adult Attachment Projective Picture System (AAP). Unlike the LEAS, the AAP is specifically designed to trigger attachment distress. In both conditions, the narratives were evaluated using the LEAS scoring system. Additionally, we assessed the impact of childhood trauma on affect-centered mentalization with the Childhood Trauma Questionnaire (CTQ). Results While the non-clinical sample displayed the same level of affect-centered mentalization in both conditions, the majority of the clinical sample reached higher scores in the attachment distress condition. There was no strong relationship between reported trauma and mentalization scores. Discussion Our findings lend strong empirical support to the assumption that affect-centered mentalization is modulated by attachment-related distress. Several possible explanations for the differences between and within the clinical and the non-clinical sample are discussed.
    • A diffusion-matched principal component analysis (DM-PCA) based two-channel denoising procedure for high-resolution diffusion-weighted MRI

      Chen, Nan-kuei Nan-kuei; Chang, Hing-Chiu; Bilgin, Ali; Bernstein, Adam; Trouard, Theodore P.; Univ Arizona, Dept Biomed Engn; Univ Arizona, Dept Med Imaging; Univ Arizona, Dept Elect & Comp Engn; Univ Arizona, Inst BIO5; Univ Arizona, Evelyn F McKnight Brain Inst (PUBLIC LIBRARY SCIENCE, 2018-04-25)
      Over the past several years, significant efforts have been made to improve the spatial resolution of diffusion-weighted imaging (DWI), aiming at better detecting subtle lesions and more reliably resolving white-matter fiber tracts. A major concern with high-resolution DWI is the limited signal-to-noise ratio (SNR), which may significantly offset the advantages of high spatial resolution. Although the SNR of DWI data can be improved by denoising in post-processing, existing denoising procedures may potentially reduce the anatomic resolvability of high-resolution imaging data. Additionally, non-Gaussian noise induced signal bias in low-SNR DWI data may not always be corrected with existing denoising approaches. Here we report an improved denoising procedure, termed diffusion-matched principal component analysis (DM-PCA), which comprises 1) identifying a group of (not necessarily neighboring) voxels that demonstrate very similar magnitude signal variation patterns along the diffusion dimension, 2) correcting low-frequency phase variations in complex-valued DWI data, 3) performing PCA along the diffusion dimension for real-and imaginary-components (in two separate channels) of phase-corrected DWI voxels with matched diffusion properties, 4) suppressing the noisy PCA components in real-and imaginary-components, separately, of phase-corrected DWI data, and 5) combining real-and imaginary-components of denoised DWI data. Our data show that the new two-channel (i.e., for real-and imaginary-components) DM-PCA denoising procedure performs reliably without noticeably compromising anatomic resolvability. Non-Gaussian noise induced signal bias could also be reduced with the new denoising method. The DM-PCA based denoising procedure should prove highly valuable for high-resolution DWI studies in research and clinical uses.
    • Performance of next-generation sequencing on small tumor specimens and/or low tumor content samples using a commercially available platform

      Morris, Scott; Subramanian, Janakiraman; Gel, Esma; Runger, George; Thompson, Eric; Mallery, David; Weiss, Glen; Univ Arizona, Coll Med Phoenix (PUBLIC LIBRARY SCIENCE, 2018-04-27)
      Background Next generation sequencing tests (NGS) are usually performed on relatively small core biopsy or fine needle aspiration (FNA) samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform. Methods 2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed. Results 6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1-3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm(2) provides a good margin of error for specimens to yield adequate drug association results. Conclusions Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.
    • Implications from GW170817 and I-Love-Q relations for relativistic hybrid stars

      Paschalidis, Vasileios; Yagi, Kent; Alvarez-Castillo, David; Blaschke, David B.; Sedrakian, Armen; Univ Arizona, Dept Astron & Phys, Theoret Astrophys Program (AMER PHYSICAL SOC, 2018-04-23)
      Gravitational wave observations of GW170817 placed bounds on the tidal deformabilities of compact stars, allowing one to probe equations of state for matter at supranuclear densities. Here we design new parametrizations for hybrid hadron-quark equations of state, which give rise to low-mass twin stars, and test them against GW170817. We find that GW170817 is consistent with the coalescence of a binary hybrid star-neutron star. We also test and find that the I-Love-Q relations for hybrid stars in the third family agree with those for purely hadronic and quark stars within similar to 3% for both slowly and rapidly rotating configurations, implying that these relations can be used to perform equation-of-state independent tests of general relativity and to break degeneracies in gravitational waveforms for hybrid stars in the third family as well.
    • Bio-inspired imager improves sensitivity in near-infrared fluorescence image-guided surgery

      Garcia, Missael; Edmiston, Christopher; York, Timothy; Marinov, Radoslav; Mondal, Suman; Zhu, Nan; Sudlow, Gail P.; Akers, Walter J.; Margenthaler, Julie; Achilefu, Samuel; Liang, Rongguang; Zayed, Mohamed A.; Pepino, Marta Y.; Gruev, Viktor; Univ Arizona, Coll Opt Sci (OPTICAL SOC AMER, 2018-04-20)
      Image-guided surgery can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky and costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities for distinguishing cancerous from healthy tissue. Here we introduce an innovative design, comprising an artificial multispectral sensor inspired by the Morpho butterfly's compound eye, which can significantly improve image-guided surgery. By monolithically integrating spectral tapetal filters with photodetectors, we have realized a single-chip multispectral imager with 1000 x higher sensitivity and 7 x better spatial co-registration accuracy compared to clinical imaging systems in current use. Preclinical and clinical data demonstrate that this technology seamlessly integrates into the surgical workflow while providing surgeons with real-time information on the location of cancerous tissue and sentinel lymph nodes. Due to its low manufacturing cost, our bio-inspired sensor will provide resource-limited hospitals with much-needed technology to enable more accurate value-based health care. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement