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Chengetai R Mahomva,1,&ast; Kristine A Smith,1,&ast; Prince AB Minkah,2 Benjamin L Witt,3 Gretchen M Oakley,1 Richard R Orlandi,1 Jeremiah A Alt,1,2,4 Abigail Pulsipher1,2,4 1Department of Otolaryngology-Head and Neck Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA; 2Department of Molecular Pharmaceutics, University of Utah College of Pharmacy, Salt Lake City, UT, USA; 3Cytopathology Section, University of Utah School of Medicine, Salt Lake City, UT, USA; 4Utah Center for Nanomedicine, University of Utah College of Pharmacy, Salt Lake City, UT, USA&ast;These authors contributed equally to this workCorrespondence: Abigail Pulsipher, University of Utah School of Medicine, Department of Otolaryngology-Head and Neck Surgery, 36 South Wasatch Drive, Salt Lake City, UT, 84112, USA, Tel +1 4342493268, Fax +1 8015855744, Email abigail.pulsipher@utah.eduBackground: CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown. This study sought to determine the transcriptional changes in CCL19, its receptors, and associated cytokines and their association with disease severity in CRS.Methods: A clinical database of control subjects and patients with CRS was examined. Lund-Kennedy, Lund-Mackay, Sinonasal Outcomes Test 22 (SNOT-22), and rhinosinusitis disability index (RSDI) scores were collected at enrollment. mRNA was extracted from sinonasal tissues and subjected to multiplex gene expression analysis. Gene transcript differences between patients with CRS and controls were compared and correlated with disease severity metrics. Immunohistochemical analyses of CCL19, CCR7, and CCRL1 were conducted to compare differences in protein expression between cohorts. A subgroup analysis was performed to compare transcriptional and protein expression difference between patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls.Results: Thirty-eight subjects (control group, n=7; CRS group, n=31) were included in this study. CCRL1 (p=0.0093) and CCR7 (p=0.017) levels were significantly elevated in CRS compared to those in controls. CCL19 (p=0.038) and CCR7 (p=0.0097) levels were elevated in CRSwNP and CCRL1 was elevated in CRSsNP (p=0.0004). CCR7 expression was significantly elevated in sinonasal epithelial cells in CRSwNP (p=0.04). CCL19 expression was positively correlated with TNFA expression (p< 0.0002). CCL19 and CCR7 expression was positively correlated with SNOT-22 and RSDI scores (p< 0.05).Conclusion: CCL19 and CCR7 may modulate TNF-α-driven pro-inflammatory signaling and contribute to increased disease severity in CRS. Mechanistic studies are required to further elucidate the role of CCRL1 in CRS.Keywords: chronic rhinosinusitis with nasal polyps, chemokines, cytokines, gene expression, protein expression

Robert W Arnold,1 Samuel J Martin,2 Joshua R Beveridge,3 Andrew W Arnold,4 Stephanie L Arnold,4 Nathanael R Beveridge,5 Kyle A Smith1,6 1Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, 99508, USA; 2Loma Linda Medical School, Loma Linda, CA, USA; 3Idaho College of Osteopathic Medicine, Boise, ID, USA; 4Ascension Genesys Residency Program, Grand Blanc, MI, USA; 5US Airforce Academy, Colorado Springs, CO, USA; 6Accurate Vision, Anchorage, AK, USACorrespondence: Robert W ArnoldAlaska Children’s EYE & Strabismus, 3500 Latouche Street #280, Anchorage, AK, 99508, USATel +1(907)561-1917Fax +1 9075635373Email eyedoc@alaska.netBackground: Handheld devices can automatically give an estimate of refraction. The established method for refraction comparison using spherical equivalent (M) and J0, J45 vector transformations by Bland–Altman analysis is too complex for non-eye doctors involved with vision screening and remote vision clinics. Therefore, a simpler comparison technique was developed.Methods: Based on the spectacle limit to resolve grade A 1 logMAR, B 3 logMAR and C 6 logMAR blur, J0, J45, and M are combined into the Alaska Blind Child Discovery (ABCD) composite ellipsoid GRADE system. Pediatric eye patients had confirmatory examination after dry refraction with three portable autorefractors: Plusoptix, 2WIN and Retinomax. The refractions were then compared using both Bland–Altman and ABCD composite. Performance to detect AAPOS amblyopia risk factors was also assessed.Results: A total of 202 children, mean age seven years, 28% high spectacle need and 43% AAPOS 2013 amblyopia risk factors showed high correlation with cycloplegic refraction (intraclass correlation 0.49 to 0.90) for sphere, J0 and J45 spectacle components. Plusoptix had more (10%) inconclusives due to patients out-of-range. The Retinomax was unable to screen some younger children and was less reliable for sphere but gave more precise astigmatism estimates. The proportion of autorefractions expected to give GRADE A/B high-need patients acuity improvement to 20/40 would be 41% for Plusoptix, 39% for 2WIN and 65% for Retinomax. Sensitivity/specificity for amblyopia risk factor detection was 80%/83% for Plusoptix, 72%/88% for 2WIN and 84%/73% for Retinomax.Conclusion: The simplified spectacle comparison resembled Bland–Altman and could assist lay vision screeners and non-eye doctors attempting remote spectacle donation worldwide.Keywords: spectacles, remote dispensing, autorefractors, validation

Robert W Arnold,1 Joshua S Beveridge,1 Samuel J Martin,1 Nathanael R Beveridge,1 Elise J Metzger,2 Kyle A Smith3 1The Alaska Blind Child Discovery, Anchorage, AK 99508, USA; 2Grace Christian School, Anchorage, AK, USA; 3Kyle Smith, Accurate Vision, Anchorage, AK, USACorrespondence: Robert W ArnoldThe Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, 3500 Latouche #280, Anchorage, AK 99508, USATel +1 907 561-1917Fax +1 907 563-5373Email eyedoc@alaska.netBackground: Portable autorefractors can estimate refractive error in remote locations, but sphero-cylinder comparison and donated-spectacle dispensing are not yet simple.Methods: Normal astigmats determined best corrected acuity, then degraded 1 logMAR (Grade A), 3 logMAR (Grade B), and 6 logMAR (Grade C) to determine limits of astigmatism axis and power at these levels. The cylindrical refraction was vector transformed with J0 on the abscissa and J45 on the ordinate.Results: Ten subjects produced multiple refractions at the interfaces of Grades A, B, and C representing ovals on the J0 and J45 coordinates. When rotated, the vertical axis represented 45° or 135°, the horizontal long axis was 1.6× the short axis. The size of the ovals positively correlated with cylinder power. Given a target refraction, the comparability of a candidate lens was demonstrated on our interactive database yielding a simple A, B, C, or worse grade for cylinder, spherical equivalent, and pupillary diameter.Conclusion(s)/Relevance: Inputting a remote autorefraction, pupillary diameter and age as target and a donated spectacle as the candidate with a “B” grade similarity would be expected to attain 20/40 acuity (3 logMAR degrade) if best corrected visual acuity was 20/20. This practical Excel database could facilitate widespread remote lay dispensing of the cylinder as well as spherical spectacles. The grade similarity can also compare refracting tools such as photoscreeners and hand-held autorefractors.Clinical Trials Registry: NCT04297969.Keywords: donated recyled spectacles, remote dispensing, portable autorefraction, vision screen validation, forensic optometry

Andrew W Arnold,1 Andrew M Eller,2 Kyle A Smith,3 Robin L Grendahl,4 R Kevin Winkle,4 Robert W Arnold4 1Pacific Northwest University College of Osteopathic Medicine, Yakima, WA, USA; 2University of Arkansas Medical School, Little Rock, AR, USA; 3Accurate Vision Center, Anchorage, AK, USA; 4Alaska Children’s Eye & Strabismus, Anchorage, AK 99508, USACorrespondence: Robert W ArnoldAlaska Children’s Eye & Strabismus, 3500 Latouche #280, Anchorage, AK 99508, USATel +1 907 561-1917Fax +1 907 563-5373Email eyedoc@alaska.netBackground: Optic nerve hypoplasia (ONH), one of the most common causes of pediatric blindness in developed countries, has been difficult to directly quantify. We sought to measure optic nerve size in Alaskan pediatric patients with optic nerve hypoplasia using ultra-widefield fundus imaging.Methods: Adult and pediatric patients underwent conventional ultra widefield fundus imaging (OPTOS, Dunfermline, Scotland) with manual image processing to determine optic nerve size validated against refractive error and nystagmus and compared to optical spectral domain tomography. De-identified cases were then compared relative to visual acuity and birth prevalence.Results: In Alaska’s only pediatric ophthalmology outreach clinic, 108 cases of ONH less than 20 years old were clinically identified with 80 having ultra-widefield analysis. Median horizontal optic nerve diameter for 135 normals was 1.70 (95% C.I. 1.49, 2.14) whereas in patients clinically diagnosed with optic nerve hypoplasia was 1.23 (95% C.I 0.38, 1.45). Visual acuity (20/y) was related to horizontal optic nerve diameter (x) by y = 187 x-4.1. Horizontal nerve diameter h could be estimated from vertical nerve diameter v by h = 0.73v + 0.3 even in nystagmus patients. From 108 with ONH, 6 had threshold retinopathy of prematurity, 12 profound nystagmus, 32 legally blind, 6 with septo-optic dysplasia, and 5 with fetal alcohol syndrome. ONH is very prevalent in Alaska occurring at least 8– 10 per 10,000 births.Conclusion: Compared to vertical diameter, horizontal diameter was more distinctive of optic nerve hypoplasia and more perturbed by nystagmus. Both were independent of refractive error. When hand-held, spectral domain OCT is not convenient, ultra-widefield fundus analysis is recommended for direct estimation of optic nerve size in children and adults. Optic nerve hypoplasia is prevalent in Alaskan children.Keywords: pediatric blindness, optic nerve, birth defect, dysmorphic, retinopathy of prematurity, septo-optic dysplasia, OPTOS

Kyle A Smith,1 Alex G Damarjian,2 Aaron Molina,3 Robert W Arnold41Clinical Optometry Department, Accurate Vision Clinic, Anchorage, AK, USA; 2Technology and Humanities Department, Illinois Institute of Technology, Chicago, IL, USA; 3Programming Department, PDI Check, Anchorage, AK, USA; 4The Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, USASignificance: A Nintendo® 3DS™ game can reliably test monocular near acuity, stereopsis and color without the need for occlusion patches or goggles.Purpose: We developed dynamic, forced-multiple choice games to measure monocular near acuity, color vision and stereopsis on the autostereoscopic barrier screen of the Nintendo 3DS gaming system.Methods: In an institutional review board-approved study, pediatric and adult patients and normal subjects performed routine patched near visual acuity, Ishahara’s color test and Stereo Fly tests. Then each subject performed a two-phase orientation and testing game, “PDI Check”, on a Nintendo 3DS.Results: Forty-five patients aged 5–60 years completed the routine and Nintendo near tests, resulting in positive, consistent, discriminatory correlation functions. From ROC curves, referral criteria were determined to separate poor from fair-to-normal monocular acuity with 98% sensitivity and 100% specificity, stereoacuity with 80% sensitivity and 97% specificity, and color with 83% sensitivity and 100% specificity.Conclusion: The Nintendo 3DS game PDI Check can provide consistent near vision testing via a dynamic, randomized method that does not require goggles for stereo, and does not require patching to assure monocular testing.Keywords: near sensory testing, video game, autostereoscopic barrier screen, monocular visual acuity, stereopsis, dynamic color test

The Hawaiian mesopelagic boundary community is a slope-associated assemblage of micronekton that undergoes diel migrations along the slopes of the islands, residing at greater depths during the day and moving upslope to forage in shallower water at night. The timing of these migrations may be influenced by environmental factors such as moon phase or ambient light. To investigate the movements of this community, we examined echo intensity data from acoustic Doppler current profilers (ADCPs) deployed at shallow and deep sites on the southern slope of Oahu, Hawaii. Diel changes in echo intensity (and therefore in estimated backscatter) were observed and determined to be caused, at least in part, by the horizontal migration of the mesopelagic boundary community. Generalized additive modeling (GAM) was used to assess the impact of environmental factors on the migration timing. Sunset time and lunar illumination were found to be significant factors. Movement speeds of the mesopelagic boundary community were estimated at 1.25–1.99 km h-1 (35–55 cm s-1). The location at which the migrations were observed is the future site of a seawater air conditioning system, which will cause artificial upwelling at our shallow observation site and may cause animal entrainment at the seawater intake near our deep water observation site. This study is the first to observe the diel migration of the mesopelagic boundary community on southern Oahu in both deep and shallow parts of the habitat, and it is also the first to examine migration trends over long time scales, which allows a better assessment of the effects of seasons and lunar illumination on micronekton migrations. Understanding the driving mechanisms of mesopelagic boundary community behavior will increase our ability to assess and manage coastal ecosystems in the face of increasing anthropogenic impacts.

Michelle A Donaghy,1 Kylie A Smith,2,3 1Faculty of Health Sciences, Australian Catholic University, North Sydney, NSW, 2Murdoch Childrens Research Institute, Royal Childrens Hospital, 3Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia Abstract: Stuttering is a speech disorder, with onset often occurring in the preschool years. The prevalence of stuttering in young children is much higher than that in the general population, suggesting a high rate of recovery. However, we are unable to predict which children will recover without treatment, and it is widely acknowledged that stuttering therapy during childhood provides the best safeguard against chronic stuttering. This review reports on current evidence-based stuttering treatment options for preschoolers through to adolescents. We discuss the clinical challenges associated with treating pediatric clients who stutter at different stages of development and explore potential areas of treatment research that might serve to advance current clinical practice in the future. Keywords: stuttering, stammering, pediatric, therapy, evidence based

We employ synchrotron-based near-field infrared spectroscopy to reveal the vibrational properties of bulk, few-sheet, and single-sheet members of the MPS3 (M=Mn, Fe, Ni) family of materials and compare our findings with complementary lattice dynamics calculations. MnPS3 and the Fe analog are similar in terms of their symmetry crossovers, from C2/m to P3¯1m, as the monolayer is approached. These states differ as to the presence of a C3 rotation around the metal center. On the other hand, NiPS3 does not show a symmetry crossover, and the lack of a Bu symmetry mode near 450 cm-1 suggests that C3 rotational symmetry is already present, even in the bulk material. We discuss these findings in terms of local symmetry and temperature effects as well as the curious relationship between these symmetry transformations and those that take place under pressure.

Ferroic materials are well known to exhibit heterogeneity in the form of domain walls. Understanding the properties of these boundaries is crucial for controlling functionality with external stimuli and for realizing their potential for ultra-low power memory and logic devices as well as novel computing architectures. In this work, we employ synchrotron-based near-field infrared nano-spectroscopy to reveal the vibrational properties of ferroelastic (90[Formula: see text] ferroelectric) domain walls in the hybrid improper ferroelectric Ca[Formula: see text]Ti[Formula: see text]O[Formula: see text]. By locally mapping the Ti-O stretching and Ti-O-Ti bending modes, we reveal how structural order parameters rotate across a wall. Thus, we link observed near-field amplitude changes to underlying structural modulations and test ferroelectric switching models against real space measurements of local structure. This initiative opens the door to broadband infrared nano-imaging of heterogeneity in ferroics.

We measured the near-field infrared response of MnPS3 in bulk, few-, and single-layer form and compared our findings with traditional far-field vibrational spectroscopies, a symmetry analysis, and first-principles lattice dynamics calculations. Trends in the Bu mode near 450cm-1 are striking, with the disappearance of this structure in the thinnest sheets. Combined with the amplified response of the activated Ag mode and analysis of the Au+Bu features, we find that symmetry is unexpectedly increased in few- and single-sheet MnPS3 due to a restoration of the threefold axes of rotation. Monoclinicity in this system is therefore a consequence of the long-range stacking pattern and temperature rather than local structure.

Secondary organic aerosol (SOA) is a complex mixture of hundreds of semi-volatile to extremely low-volatility organic compounds that are chemically processed in the atmosphere, including via heterogeneous oxidation by gas-phase radicals. Relative humidity (RH) has a substantial impact on particle phase, which can affect how SOA evolves in the atmosphere. In this study, SOA from dark α-pinene ozonolysis is heterogeneously aged by OH radicals in a flow tube at low and high RH. At high RH (RH Combining double low line 89%) there is substantial loss of particle volume ( ĝ1/4 60%) at an equivalent atmospheric OH exposure of 3 weeks. In contrast, at low RH (RH Combining double low line 25%) there is little mass loss ( < 20%) at the same OH exposure. Mass spectra of the SOA particles were measured as a function of OH exposure using a vacuum ultraviolet aerosol mass spectrometer (VUV-AMS). The mass spectra observed at low RH overall exhibit minor changes with oxidation and negligible further changes above an OH exposure Combining double low line 2×1012moleculecm-3s suggesting limited impact of oxidation on the particle composition. In contrast, the mass spectra observed at high RH exhibit substantial and continuous changes as a function of OH exposure. Further, at high RH clusters of peaks in the mass spectra exhibit unique decay patterns, suggesting different responses of various species to oxidation. A model of heterogeneous oxidation has been developed to understand the origin of the difference in aging between the low- and high-RH experiments. Differences in diffusivity of the SOA between the low- and high-RH experiments alone can explain the difference in compositional change but cannot explain the difference in mass loss. Instead, the difference in mass loss is attributable to RH-dependent differences in the OH uptake coefficient and/or the net probability of fragmentation, with either or both larger at high RH compared to low RH. These results illustrate the important impact of relative humidity on the fate of SOA in the atmosphere.

In this paper we provide evidence of the benefits of an approach which combines data mining and mathematical programming to determining the premium to charge automobile insurance policy holders in order to arrive at an optimal portfolio. An non-linear integer programming formulation is proposed to determine optimal premiums based on the insurer's need to find a balance between profitability and market share. The non-linear integer programming approach to solving this problem is used within a data mining framework which consists of three components: classifying policy holders into homogenous risk groups and predicting the claim cost of each group using k-means clustering; determining the price sensitivity (propensity to pay) of each group using neural networks; and combining the results of the first two components to determine the optimal premium to charge. We have earlier presented the results of the first two components. In this paper we present the results of the third component. Using our approach, we have been able to increase revenue without affecting termination rates and market share. Keywords: data mining; insurance; clustering; neural networks; integer programming; optimisation

Stromal cell-derived factor 1 (SDF-1) is known to influence bone marrow stromal cell (BMSC) migration, osteogenic differentiation, and fracture healing. We hypothesize that SDF-1 mediates some of its effects on BMSCs through epigenetic regulation, specifically via microRNAs (miRNAs). MiRNAs are small non-coding RNAs that target specific mRNA and prevent their translation. We performed global miRNA analysis and determined several miRNAs were differentially expressed in response to SDF-1 treatment. Gene Expression Omnibus (GEO) dataset analysis showed that these miRNAs play an important role in osteogenic differentiation and fracture healing. KEGG and GO analysis indicated that SDF-1 dependent miRNAs changes affect multiple cellular pathways, including fatty acid biosynthesis, thyroid hormone signaling, and mucin-type O-glycan biosynthesis pathways. Furthermore, bioinformatics analysis showed several miRNAs target genes related to stem cell migration and differentiation. This study's findings indicated that SDF-1 induces some of its effects on BMSCs function through miRNA regulation.

Background: Effective management of post-surgical pain in knee arthroscopy is crucial for early rehabilitation of patients. This study is aimed to analyse the potency of fentanyl when administered intraarticularly alone and in combination with dexmedetomidine for postsurgical analgesia after knee arthroscopy. Methods: Prospective double-blinded randomized controlled study included 60 patients of elective knee arthroscopy. The patients were classified in group I (100-mcg fentanyl) and group II (treated with 100-mcg + 50-μg dexmedetomidine). VAS score and time for foremost requirement of analgesia was documented. Results: The difference in the VAS scores across the two groups was statistically significant for initial 6 hours. In groups I, 18 (60%), and II, 4 (13.33%) patients requested analgesia within 6 hours, whereas 12(40%) and 26(86.67%) patients requested analgesia after 6 hours, respectively. For the foremost requirement of analgesia within and after 6 hours, the difference between the number of patients in group I was statistically insignificant (P = 0.1967), whereas that in group II was statistically significant (P 6-hour-long analgesia, lowers degree of postsurgical pain, and requirement for postsurgical analgesia. Therefore, mentioned combination is highly effective and better analgesic than fentanyl alone.