279 results on '"Hunter DA"'
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2. Legacy extragalactic UV survey (LEGUS) with the hubble space telescope. I. Survey description
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Calzetti, D, Lee, JC, Sabbi, E, Adamo, A, Smith, LJ, Andrews, JE, Ubeda, L, Bright, SN, Thilker, D, Aloisi, A, Brown, TM, Chandar, R, Christian, C, Cignoni, M, Clayton, GC, Da Silva, R, De Mink, SE, Dobbs, C, Elmegreen, BG, Elmegreen, DM, Evans, AS, Fumagalli, M, Gallagher, JS, Gouliermis, DA, Grebel, EK, Herrero, A, Hunter, DA, Johnson, KE, Kennicutt, RC, Kim, H, Krumholz, MR, Lennon, D, Levay, K, Martin, C, Nair, P, Nota, A, Östlin, G, Pellerin, A, Prieto, J, Regan, MW, Ryon, JE, Schaerer, D, Schiminovich, D, Tosi, M, Van Dyk, SD, Walterbos, R, Whitmore, BC, and Wofford, A
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© 2015. The American Astronomical Society. All rights reserved. The Legacy ExtraGalactic UV Survey (LEGUS) is a Cycle 21 Treasury program on the Hubble Space Telescope aimed at the investigation of star formation and its relation with galactic environment in nearby galaxies, from the scales of individual stars to those of ∼kiloparsec-size clustered structures. Five-band imaging from the nearultraviolet to the I band with the Wide-Field Camera 3 (WFC3), plus parallel optical imaging with the Advanced Camera for Surveys (ACS), is being collected for selected pointings of 50 galaxies within the local 12 Mpc. The filters used for the observations with the WFC3 are F275W (λ2704 A˚), F336W(λ3355 A˚), F438W(λ4325 A˚), F555W(λ5308 A˚), and F814W(ë8024 A˚); the parallel observations with the ACS use the filters F435W (λ4328 A˚), F606W(λ5921 A˚), and F814W(λ8057 A˚). The multiband images are yielding accurate recent (≲50 Myr) star formation histories from resolved massive stars and the extinction-corrected ages and masses of star clusters and associations. The extensive inventories of massive stars and clustered systems will be used to investigate the spatial and temporal evolution of star formation within galaxies. This will, in turn, inform theories of galaxy evolution and improve the understanding of the physical underpinning of the gas-star formation relation and the nature of star formation at high redshift. This paper describes the survey, its goals and observational strategy, and the initial scientific results. Because LEGUS will provide a reference survey and a foundation for future observations with the James Webb Space Telescope and with ALMA, a large number of data products are planned for delivery to the community.
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- 2015
3. Impacts of duty belts and load placement on police officers: A systematic review
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Berner Nolan, Biilmann Christopher, Hunter Daniel, Canetti Elisa, Schram Ben, Dawes Jay, Lockie Robert, and Orr Robin
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law enforcement ,load carriage ,accoutrements belt ,load bearing vest ,duty loads ,occupational health ,back injury ,injury prevention ,Social pathology. Social and public welfare. Criminology ,HV1-9960 - Abstract
Background. Law enforcement officers (LEOs) wear duty belts to hold the specialised equipment required to complete their daily occupational tasks. The aim of this review was to identify, collect, and synthesize research investigating the impacts of duty belts and load placement on LEOs. Methods: A systematic review, registered with the Open Science Framework, was conducted following the Preferred Reporting Items for Systematic Reviews guidelines. Five databases were searched (PubMed, Embase, CINAHL, SPORTDiscus, and Web of Science) with identified studies considered against eligibility criteria. Included studies were critically appraised by two reviewers independently using the Joanna Briggs Institute checklist or the Mixed Method Appraisal Tool. Results: Ten studies (mean appraisal score = 79.8%; Kappa agreement = 0.73) informed the review revealing two main emerging themes; occupational impacts (task performance, vehicle duties, and weapon draw time), and movement impacts (balance, gait, and jump-based movements). Nine studies found duty belts and equipment loads, regardless of placement, negatively impacted LEO occupational tasks and movements in general. There were some differences in the nature of the impacts (e.g., areas of pressure with different systems). One study found no differences in performance between hip versus thigh holsters. Conclusions: The evidence suggests that LEO duty belts, their attachments, and the loads imparted by their equipment have a negative impact on performance of occupational tasks as well as officer movement, increasing injury potential. There were some differences in impacts based on load placement warranting consideration and further research.
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- 2024
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4. Legacy ExtraGalactic UV Survey with The $\textit{Hubble Space Telescope}$: Stellar Cluster Catalogs and First Insights Into Cluster Formation and Evolution in NGC 628
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Adamo, A, Ryon, JE, Messa, M, Kim, H, Grasha, K, Cook, DO, Calzetti, D, Lee, JC, Whitmore, BC, Elmegreen, BG, Ubeda, L, Smith, LJ, Bright, SN, Runnholm, A, Andrews, JE, Fumagalli, M, Gouliermis, DA, Kahre, L, Nair, P, Thilker, D, Walterbos, R, Wofford, A, Aloisi, A, Ashworth, G, Brown, TM, Chandar, R, Christian, C, Cignoni, M, Clayton, GC, Dale, DA, Mink, SED, Dobbs, C, Elmegreen, DM, Evans, AS, III, JSG, Grebel, EK, Herrero, A, Hunter, DA, Johnson, KE, Kennicutt, RC, Krumholz, MR, Lennon, D, Levay, K, Martin, C, Nota, A, Ostlin, G, Pellerin, A, Prieto, J, Regan, MW, Sabbi, E, Sacchi, E, Schaerer, D, Shabani, DSF, Tosi, M, Dyk, SDV, Zackrisson, E, Kennicutt, Robert [0000-0001-5448-1821], and Apollo - University of Cambridge Repository
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stars: formation ,galaxies: individual (NGC 628, M74) ,Astrophysics::High Energy Astrophysical Phenomena ,galaxies: star formation ,galaxies: star clusters: general ,Astrophysics::Solar and Stellar Astrophysics ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Astrophysics::Galaxy Astrophysics - Abstract
We report the large effort that is producing comprehensive high-level young star cluster (YSC) catalogs for a significant fraction of galaxies observed with the Legacy ExtraGalactic UV Survey (LEGUS) Hubble treasury program. We present the methodology developed to extract cluster positions, verify their genuine nature, produce multiband photometry (from NUV to NIR), and derive their physical properties via spectral energy distribution fitting analyses. We use the nearby spiral galaxy NGC 628 as a test case for demonstrating the impact that LEGUS will have on our understanding of the formation and evolution of YSCs and compact stellar associations within their host galaxy. Our analysis of the cluster luminosity function from the UV to the NIR finds a steepening at the bright end and at all wavelengths suggesting a dearth of luminous clusters. The cluster mass function of NGC 628 is consistent with a power-law distribution of slopes $\sim -2$ and a truncation of a few times 105 ${M}_{\odot }$. After their formation, YSCs and compact associations follow different evolutionary paths. YSCs survive for a longer time frame, confirming their being potentially bound systems. Associations disappear on timescales comparable to hierarchically organized star-forming regions, suggesting that they are expanding systems. We find mass-independent cluster disruption in the inner region of NGC 628, while in the outer part of the galaxy there is little or no disruption. We observe faster disruption rates for low mass (≤104 ${M}_{\odot }$) clusters, suggesting that a mass-dependent component is necessary to fully describe the YSC disruption process in NGC 628., A.A. acknowledges partial support from the Swedish Royal Academy. G.A. acknowledges support from the Science and Technology Facilities Council (ST/L00075X/1 and ST/M503472/1). C.D. acknowledges funding from the FP7 ERC starting grant LOCALSTAR (no. 280104). M.F. acknowledges support by the Science and Technology Facilities Council (grant number ST/L00075X/1). D.A.G. kindly acknowledges financial support by the German Research Foundation (DFG) through program GO 1659/3-2. A.H. thanks the Spanish MINECO for grant AYA2015-68012-c2-1. These observations are associated with program # 13364. Support for program # 13364 was provided by NASA through a grant from the Space Telescope Science Institute. Based on observations obtained with the NASA/ESA Hubble Space Telescope, at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.
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- 2017
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5. Inhibition of Topoisomerases by Metal Thiosemicarbazone Complexes
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Xiaohua Jiang, Lauren A. Fielding, Hunter Davis, William Carroll, Edward C. Lisic, and Joseph E. Deweese
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thiosemicarbazone ,topoisomerase ,antitumor ,bis-thiosemicarbazone ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Topoisomerases, common targets for anti-cancer therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effects of thiosemicarbazones (TSC) and metal–TSC complexes have been demonstrated to target several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition of topoisomerase II. The processes by which metal–TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal–TSCs that inhibit various types of human topoisomerases, and we note some of the key unanswered questions regarding this interesting class of diverse compounds.
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- 2023
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6. Reproductive isolation caused by azoospermia in sterile male hybrids of Drosophila
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Hunter Davis, Nicholas Sosulski, and Alberto Civetta
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azoospermia ,Drosophila ,hybrid male sterility ,speciation ,sperm transfer ,Ecology ,QH540-549.5 - Abstract
Abstract Recently diverged populations in the early stages of speciation offer an opportunity to understand mechanisms of isolation and their relative contributions. Drosophila willistoni is a tropical species with broad distribution from Argentina to the southern United States, including the Caribbean islands. A postzygotic barrier between northern populations (North America, Central America, and the northern Caribbean islands) and southern populations (South American and the southern Caribbean islands) has been recently documented and used to propose the existence of two different subspecies. Here, we identify premating isolation between populations regardless of their subspecies status. We find no evidence of postmating prezygotic isolation and proceeded to characterize hybrid male sterility between the subspecies. Sterile male hybrids transfer an ejaculate that is devoid of sperm but causes elongation and expansion of the female uterus. In sterile male hybrids, bulging of the seminal vesicle appears to impede the movement of the sperm toward the sperm pump, where sperm normally mixes with accessory gland products. Our results highlight a unique form of hybrid male sterility in Drosophila that is driven by a mechanical impediment to transfer sperm rather than by an abnormality of the sperm itself. Interestingly, this form of sterility is reminiscent of a form of infertility (azoospermia) that is caused by lack of sperm in the semen due to blockages that impede the sperm from reaching the ejaculate.
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- 2020
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7. The nature of the extended H I gas around NGC 4449: The Dr. Jekyll Mr. Hyde of irregular galaxies
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Hunter, DA, Wilcots, EM, van Woerden, H, Gallagher, JS, Kohle, S, and Kapteyn Astronomical Institute
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LARGE-SAMPLE ,galaxies, irregular ,DISKS ,NGC-3077 ,ORIGIN ,CLOUDS ,Astrophysics::Cosmology and Extragalactic Astrophysics ,galaxies, ISM ,HYDROGEN ,galaxies, kinematics and dynamics ,SIMULATIONS ,galaxies, individual (NGC 4449) ,MAGELLANIC STREAM ,M-81 ,Astrophysics::Solar and Stellar Astrophysics ,EMISSION ,Astrophysics::Galaxy Astrophysics - Abstract
We present interferometric H I 21 cm line observations of the extended gas around the irregular galaxy NGC 4449 covering 67' on the sky at a resolution of similar to 1'. The main star-forming body of NGC 4449 is relatively normal for a Magellanic irregular galaxy, but the galaxy is unusual in that it has two counterrotating gas systems and H I that extends to 6 times the Holmberg radius. Our new, detailed H I maps of this extended gas show that most of the extended H I is located in large, highly structured, extended clouds and very long streamers. We compare NGC 4449 with other systems in the context of possible models for the origin of these structures, the most likely of which involves an interaction with another galaxy. Thus, NGC 4449 no longer fits the standard picture of an irregular galaxy quietly evolving in isolation.
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- 1998
8. 145: GELDANAMYCIN IMPROVES FUNCTIONAL RECOVERY AFTER PERIPHERAL NERVE CRUSH IN RATS
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Sun, HH, primary, Hunter, DA, additional, Johnson, PJ, additional, and Mackinnon, SE, additional
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- 2011
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9. NEUTRAL HYDROGEN AND OPTICAL-PROPERTIES OF 3 AMORPHOUS GALAXIES
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HUNTER, DA, VANWOERDEN, H, GALLAGHER, JS, and Kapteyn Astronomical Institute
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STRUCTURE ,DWARF IRREGULAR GALAXIES ,RADIO LINES ,Astrophysics::Cosmology and Extragalactic Astrophysics ,SPECTRAL ENERGY-DISTRIBUTIONS ,DISK GALAXIES ,GALAXIES ,ON SPIRAL GALAXIES ,H-I OBSERVATIONS ,STELLAR POPULATIONS ,MAGELLANIC CLOUD ,H-1 SYNTHESIS OBSERVATIONS ,SOUTHERN SPECTROPHOTOMETRIC STANDARDS ,STAR FORMATION ,Astrophysics::Galaxy Astrophysics - Abstract
We present new interferometric H I and optical observations of three amorphous galaxies, systems with a smooth, high surface brightness but an asymmetrical distribution of light. All three galaxies are forming stars and have LMC-like emission-line ratios, low dust content, and high H I velocity dispersions. NGC 1140 has a boxy inner morphology with a hook off one corner. At low light levels unusual extensions of starlight are seen curving to the northwest and southeast. The galaxy contains a very luminous central star-forming region and a small chain of H II regions that coincide with the hook. The central H II region has broad Halpha velocity profiles (FWHM less-than-or-equal-to 140 km s-1), and it is a radio continuum source. There is a rotating H I gas disk, 40 kpc in radius, at a position angle 51-degrees from the optical major axis. The central gas ridge follows the chain of H II regions, and the H I peak is on the hook. The outer gas on the southeast side curves away from the H I major axis. The central gas density is high, and the surface density declines very slowly with radius. The rotation velocity yields a mass of 1 x 10(11) M. at 3.3 Holmberg radii (R(H)). NGC 1800 has a hook that coincides with a large H II region, and an r1/4 luminosity distribution. There are numerous H II regions along the major axis and extraordinary filaments of ionized gas. Emanating from the major axis on either side of the galaxy are Halpha fingers 750 pc long. About 2.3 kpc to the north is a web of filaments approximately 3 kpc in extent. Halpha profiles of H II regions and filaments are narrow. The H i gas disk has a position angle that is approximately 13-degrees different from that of the optical axis. There are two peaks near the center, one of which is near the largest H II region. Beyond the Holmberg radius to the west is a 6 x 10(6) M. H I cloud. Its velocity indicates a mass of approximately 6 x 10(9) M. for NGC 1800 at 1.5 R(H). At approximately R25 to the east there is a large H I shell. Also, at approximately R25 on both sides the velocity gradient switches by 90-degrees, and in the interior the rotation is about the major axis. The central gas density is low and falls off slowly. In the inner regions NGC 4670 resembles an S0/a galaxy seen rather edge-on. It contains a central supergiant H II region with very high velocity widths (FWHM less-than-or-equal-to 180 km s-1) and complex velocity structures. It is a radio continuum source as well. The H I gas is a single spherical cloud or a disk at low inclination centered on the galaxy with a slight elongation along the optical major axis and rotation about the minor axis. The central gas density is high, and there is a high degree of concentration. The rotation speed indicates a total mass of 5 x 10(10) M. at 1.1 R(H). We compare these characteristics with properties of gas in the presence of stellar bar potentials, gas warps, and interacting and merging galaxy models. Although there are inconsistencies and uncertainties, we conclude that NGC 1140 is a spiral of low surface brightness that has undergone a merger, while NGC 1800 and NGC 4670 are, respectively, probably an Im system and a spiral that had an encounter of the Noguchi (1988a) kind.
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- 1994
10. 74A: SUPPLEMENTATION OF ACELLULAR NERVE GRAFTS WITH MOTOR AND SENSORY SCHWANN CELLS ENHANCES PERIPHERAL NERVE REGENERATION
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Santosa, KB, primary, Jesuraj, NJ, additional, Moore, AM, additional, MacEwan, M, additional, Ray, WZ, additional, Kale, S, additional, Hunter, DA, additional, Flagg, ER, additional, Nicoson, M, additional, Johnson, PJ, additional, and Mackinnon, SE, additional
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- 2010
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11. 211B: PROCESSED ALLOGRAFT VERSUS COLD-PRESERVATION ON NERVE REGENERATION: A COMPARISON STUDY
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Moore, AM, primary, Nicoson, MC, additional, Chenard, K, additional, Santosa, K, additional, Kasukurthi, R, additional, Hunter, DA, additional, Johnson, PJ, additional, Mackinnon, SE, additional, and Borschel, GH, additional
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- 2010
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12. 75A: UTILIZATION OF REVERSE END TO SIDE NEURORRHAPHY IN THE MANAGEMENT OF PROXIMAL NERVE INJURIES
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Kale, SS, primary, MacKinnon, SE, additional, Johnson, PJ, additional, Tong, AY, additional, Hunter, DA, additional, and Nicoson, MC, additional
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- 2010
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13. Presence of the amphibian chytrid fungus Batrachochytrium dendrobatidis in threatened corroboree frog populations in the Australian Alps
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Hunter, DA, primary, Speare, R, additional, Marantelli, G, additional, Mendez, D, additional, Pietsch, R, additional, and Osborne, W, additional
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- 2009
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14. Repair of motor nerve gaps with sensory nerve inhibits regeneration in rats.
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Brenner MJ, Hess JR, Myckatyn TM, Hayashi A, Hunter DA, and Mackinnon SE
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- 2006
15. Addition of telephone coaching to a physiotherapist-delivered physical activity program in people with knee osteoarthritis: A randomised controlled trial protocol
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Bennell Kim L, Egerton Thorlene, Bills Caroline, Gale Janette, Kolt Gregory S, Bunker Stephen J, Hunter David J, Brand Caroline A, Forbes Andrew, Harris Anthony, and Hinman Rana S
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Knee osteoarthritis (OA) is one of the most common and costly chronic musculoskeletal conditions world-wide and is associated with substantial pain and disability. Many people with knee OA also experience co-morbidities that further add to the OA burden. Uptake of and adherence to physical activity recommendations is suboptimal in this patient population, leading to poorer OA outcomes and greater impact of associated co-morbidities. This pragmatic randomised controlled trial will investigate the clinical- and cost-effectiveness of adding telephone coaching to a physiotherapist-delivered physical activity intervention for people with knee OA. Methods/Design 168 people with clinically diagnosed knee OA will be recruited from the community in metropolitan and regional areas and randomly allocated to physiotherapy only, or physiotherapy plus nurse-delivered telephone coaching. Physiotherapy involves five treatment sessions over 6 months, incorporating a home exercise program of 4–6 exercises (targeting knee extensor and hip abductor strength) and advice to increase daily physical activity. Telephone coaching comprises 6–12 telephone calls over 6 months by health practitioners trained in applying the Health Change Australia (HCA) Model of Health Change to provide behaviour change support. The telephone coaching intervention aims to maximise adherence to the physiotherapy program, as well as facilitate increased levels of participation in general physical activity. The primary outcomes are pain measured by an 11-point numeric rating scale and self-reported physical function measured by the Western Ontario and McMaster Universities Osteoarthritis Index subscale after 6 months. Secondary outcomes include physical activity levels, quality-of-life, and potential moderators and mediators of outcomes including self-efficacy, pain coping and depression. Relative cost-effectiveness will be determined from health service usage and outcome data. Follow-up assessments will also occur at 12 and 18 months. Discussion The findings will help determine whether the addition of telephone coaching sessions can improve sustainability of outcomes from a physiotherapist-delivered physical activity intervention in people with knee OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12612000308897
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- 2012
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16. Acute low back pain is marked by variability: An internet-based pilot study
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Katz Jeffrey N, Fitzmaurice Garrett M, Rainville James, Suri Pradeep, Jamison Robert N, Martha Julia, Hartigan Carol, Limke Janet, Jouve Cristin, and Hunter David J
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Pain variability in acute LBP has received limited study. The objectives of this pilot study were to characterize fluctuations in pain during acute LBP, to determine whether self-reported 'flares' of pain represent discrete periods of increased pain intensity, and to examine whether the frequency of flares was associated with back-related disability outcomes. Methods We conducted a cohort study of acute LBP patients utilizing frequent serial assessments and Internet-based data collection. Adults with acute LBP (lasting ≤3 months) completed questionnaires at the time of seeking care, and at both 3-day and 1-week intervals, for 6 weeks. Back pain was measured using a numerical pain rating scale (NPRS), and disability was measured using the Oswestry Disability Index (ODI). A pain flare was defined as 'a period of increased pain lasting at least 2 hours, when your pain intensity is distinctly worse than it has been recently'. We used mixed-effects linear regression to model longitudinal changes in pain intensity, and multivariate linear regression to model associations between flare frequency and disability outcomes. Results 42 of 47 participants (89%) reported pain flares, and the average number of discrete flare periods per patient was 3.5 over 6 weeks of follow-up. More than half of flares were less than 4 hours in duration, and about 75% of flares were less than one day in duration. A model with a quadratic trend for time best characterized improvements in pain. Pain decreased rapidly during the first 14 days after seeking care, and leveled off after about 28 days. Patients who reported a pain flare experienced an almost 3-point greater current NPRS than those not reporting a flare (mean difference [SD] 2.70 [0.11]; p < 0.0001). Higher flare frequency was independently associated with a higher final ODI score (ß [SE} 0.28 (0.08); p = 0.002). Conclusions Acute LBP is characterized by variability. Patients with acute LBP report multiple distinct flares of pain, which correspond to discrete increases in pain intensity. A higher flare frequency is associated with worse disability outcomes.
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- 2011
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17. Does lumbar spinal degeneration begin with the anterior structures? A study of the observed epidemiology in a community-based population
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Jarvik Jeffrey G, Hunter David J, Miyakoshi Asako, Suri Pradeep, Rainville James, Guermazi Ali, Li Ling, and Katz Jeffrey N
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degenerative cascade ,degeneration ,disk ,facet joint ,arthritis ,lumbar ,spine ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background- Prior studies that have concluded that disk degeneration uniformly precedes facet degeneration have been based on convenience samples of individuals with low back pain. We conducted a study to examine whether the view that spinal degeneration begins with the anterior spinal structures is supported by epidemiologic observations of degeneration in a community-based population. Methods- 361 participants from the Framingham Heart Study were included in this study. The prevalences of anterior vertebral structure degeneration (disk height loss) and posterior vertebral structure degeneration (facet joint osteoarthritis) were characterized by CT imaging. The cohort was divided into the structural subgroups of participants with 1) no degeneration, 2) isolated anterior degeneration (without posterior degeneration), 3) combined anterior and posterior degeneration, and 4) isolated posterior degeneration (without anterior structure degeneration). We determined the prevalence of each degeneration pattern by age group < 45, 45-54, 55-64, ≥65. In multivariate analyses we examined the association between disk height loss and the response variable of facet joint osteoarthritis, while adjusting for age, sex, BMI, and smoking. Results- As the prevalence of the no degeneration and isolated anterior degeneration patterns decreased with increasing age group, the prevalence of the combined anterior/posterior degeneration pattern increased. 22% of individuals demonstrated isolated posterior degeneration, without an increase in prevalence by age group. Isolated posterior degeneration was most common at the L5-S1 and L4-L5 spinal levels. In multivariate analyses, disk height loss was independently associated with facet joint osteoarthritis, as were increased age (years), female sex, and increased BMI (kg/m2), but not smoking. Conclusions- The observed epidemiology of lumbar spinal degeneration in the community-based population is consistent with an ordered progression beginning in the anterior structures, for the majority of individuals. However, some individuals demonstrate atypical patterns of degeneration, beginning in the posterior joints. Increased age and BMI, and female sex may be related to the occurrence of isolated posterior degeneration in these individuals.
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- 2011
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18. Bias in the physical examination of patients with lumbar radiculopathy
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Katz Jeffrey N, Hunter David J, Suri Pradeep, Li Ling, and Rainville James
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background No prior studies have examined systematic bias in the musculoskeletal physical examination. The objective of this study was to assess the effects of bias due to prior knowledge of lumbar spine magnetic resonance imaging findings (MRI) on perceived diagnostic accuracy of the physical examination for lumbar radiculopathy. Methods This was a cross-sectional comparison of the performance characteristics of the physical examination with blinding to MRI results (the 'independent group') with performance in the situation where the physical examination was not blinded to MRI results (the 'non-independent group'). The reference standard was the final diagnostic impression of nerve root impingement by the examining physician. Subjects were recruited from a hospital-based outpatient specialty spine clinic. All adults age 18 and older presenting with lower extremity radiating pain of duration ≤ 12 weeks were evaluated for participation. 154 consecutively recruited subjects with lumbar disk herniation confirmed by lumbar spine MRI were included in this study. Sensitivities and specificities with 95% confidence intervals were calculated in the independent and non-independent groups for the four components of the radiculopathy examination: 1) provocative testing, 2) motor strength testing, 3) pinprick sensory testing, and 4) deep tendon reflex testing. Results The perceived sensitivity of sensory testing was higher with prior knowledge of MRI results (20% vs. 36%; p = 0.05). Sensitivities and specificities for exam components otherwise showed no statistically significant differences between groups. Conclusions Prior knowledge of lumbar MRI results may introduce bias into the pinprick sensory testing component of the physical examination for lumbar radiculopathy. No statistically significant effect of bias was seen for other components of the physical examination. The effect of bias due to prior knowledge of lumbar MRI results should be considered when an isolated sensory deficit on examination is used in medical decision-making. Further studies of bias should include surgical clinic populations and other common diagnoses including shoulder, knee and hip pathology.
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- 2010
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19. Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis
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Kissin Eugene, Jonas Beth L, Pike Marilyn C, Hunter David J, Krop Julie, and McAlindon Tim
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background There are no proven therapies that modify the structural changes associated with osteoarthritis (OA). Preclinical data suggests that intra-articular recombinant human BMP-7 (bone morphogenetic protein-7) has reparative effects on cartilage, as well as on symptoms of joint pain. The objective of this study was to determine the safety and tolerability as well as dose-limiting toxicity and maximal tolerated dose of intra-articular BMP-7. The secondary objectives were to determine the effect on symptomatic responses through 24 weeks. Methods This was a Phase 1, double-blind, randomized, multi-center, placebo-controlled, single-dose escalation safety study consisting of 4 dosing cohorts in participants with knee OA. Each cohort was to consist of 8 treated participants, with treatment allocation in a 3:1 active (intra-articular BMP-7) to placebo ratio. Eligible participants were persons with symptomatic radiographic knee OA over the age of 40. The primary objective of this study was to determine the safety and tolerability of BMP-7 including laboratory assessments, immunogenicity data and radiographic assessments. Secondary objectives were to determine the proportion of participants with a 20%, 50%, and 70% improvement in the WOMAC pain and function subscales at 4, 8, 12, and 24 weeks. Other secondary outcomes included the change from baseline to 4, 8, 12, and 24 weeks for the OARSI responder criteria. Results The mean age of participants was 60 years and 73% were female. All 33 participants who were enrolled completed the study and most adverse events were mild or moderate and were similar in placebo and BMP-7 groups. The 1 mg BMP-7 group showed a higher frequency of injection site pain and there was no ectopic bone formation seen on plain x-rays. By week 12, most participants in both the BMP-7 and placebo groups experienced a 20% improvement in pain and overall the BMP-7 group was similar to placebo with regard to this measurement. In the participants who received 0.1 mg and 0.3 mg BMP-7, there was a trend toward greater symptomatic improvement than placebo. The other secondary endpoints showed similar trends including the OARSI responder criteria for which the BMP-7 groups had more responders than placebo. Conclusions There was no dose limiting toxicity identified in this study. The suggestion of a symptom response, together with the lack of dose limiting toxicity provide further support for the continued development of this product for the treatment of osteoarthritis.
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- 2010
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20. Tibiofemoral osteoarthritis affects quality of life and function in elderly Koreans, with women more adversely affected than men
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Hunter David J, Song Yeong, Seo Young-Il, Kim Hyun, Kim Inje, Jeong Jin, and Kim Dong
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background The prevalence of knee osteoarthritis(OA) in East Asia is as common for men and even higher for women than that reported in the Caucasian population. Since both population aging and economic growth have taken place at a much faster pace in Asian countries, such as South Korea, one would expect knee OA to become a major public health problem. However, few studies have examined the influence of knee OA on the quality of life (QoL) and physical function in Asia. The aim of this cross-sectional study is to investigate the influence of knee osteoarthritis (OA) on the quality of life (QoL), function and lower extremity physical performance and the gender difference in its influence in elderly community residents in Korea. Methods Participants were from the population-based Hallym Aging Study (HAS). The mean age of the 504 study subjects was 70.2 years and 274 (54%) were women. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee radiographs. Self-reported QoL and function were assessed using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12-item (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The odds ratios(ORs) for belonging to the worst quartile of WOMAC and physical performance test were calculated by logistic regression analysis in radiographic knee OA compared to non-OA after adjustment of confounders. Scores for SF-12 items were analyzed using general linear models and means adjusted for age, BMI and OA severity were compared. Results Subjects with radiographic knee OA had significantly increased OR for belonging to the worst WOMAC quartile(for pain, 2.13,95% confidence interval[CI], 1.33-3.40, for stiffness, 2.94,95% CI,1.78-4.86, and for function, 2.97, 95% CI,1.83-4.81) and significantly worse SF-12 scores compared to non-OA after adjustment of age, BMI and sex. Women had worse WOMAC and SF-12 scores compared to men, regardless of the presence of radiographic knee OA after adjustment of age, BMI and OA severity. OA subjects had significantly worse performance score for usual walk and chair stands compared to non-OA subjects, but the ORs were no more significant after adjustment of sex. Conclusions Knee OA negatively affects the QoL and physical function in both genders, but women are more adversely affected than men.
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- 2010
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21. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors
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Schernhammer Eva S, Hazra Aditi, Shima Kaori, Tanaka Noriko, Nosho Katsuhiko, Huttenhower Curtis, Baba Yoshifumi, Hunter David J, Giovannucci Edward L, Fuchs Charles S, and Ogino Shuji
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon) constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features. Design Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing). Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP), microsatellite instability, expression of TP53 (p53), CDKN1A (p21), CTNNB1 (β-catenin), PTGS2 (cyclooxygenase-2), and FASN, and mutations in KRAS, BRAF, and PIK3CA. Results Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6), and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation < 40; N = 22 (2.5%), which were far more than what could be expected by normal distribution]. LINE-1 extreme hypomethylators were significantly associated with younger patients (p = 0.0058). Residual plot by multivariate linear regression showed that LINE-1 extreme hypomethylators clustered as one distinct group, separate from the main tumor group. The multivariate linear regression model could explain 8.4% of the total variability of LINE-1 methylation (R-square = 0.084). Multivariate logistic regression models for binary LINE-1 hypomethylation outcomes (cutoffs of 40, 50 and 60) showed at most fair predictive ability (area under receiver operator characteristics curve < 0.63). Conclusions LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.
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- 2010
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22. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
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Lund Eiliv, Lenner Per, Isaacs Claudine, Hunter David J, Hoover Robert, Hankinson Susan E, Haiman Christopher A, Feigelson Heather, Dossus Laure, Clavel-Chapelon Francoise, Chanock Stephen, Calle Eugenia E, Buring Julie, Boeing Heiner, Bingham Sheila, Berg Christine, Henderson Brian E, Henderson Katherine D, Cox David G, Kaaks Rudolf, Canzian Federico, Overvad Kim, Palli Domenico, Pearce Celeste, Quiros Jose R, Riboli Elio, Stram Daniel O, Thomas Gilles, Thun Michael J, Trichopoulos Dimitrios, van Gils Carla H, and Ziegler Regina G
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
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- 2009
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23. The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale
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Eckstein Felix, Lyles Mary, DeVita Paul, Loeser Richard F, Miller Gary D, Mihalko Shannon, Legault Claudine, Messier Stephen P, Hunter David J, Williamson Jeff D, and Nicklas Barbara J
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Obesity is the most modifiable risk factor, and dietary induced weight loss potentially the best nonpharmacologic intervention to prevent or to slow osteoarthritis (OA) disease progression. We are currently conducting a study to test the hypothesis that intensive weight loss will reduce inflammation and joint loads sufficiently to alter disease progression, either with or without exercise. This article describes the intervention, the empirical evidence to support it, and test-retest reliability data. Methods/Design This is a prospective, single-blind, randomized controlled trial. The study population consists of 450 overweight and obese (BMI = 27–40.5 kg/m2) older (age ≥ 55 yrs) adults with tibiofemoral osteoarthritis. Participants are randomized to one of three 18-month interventions: intensive dietary restriction-plus-exercise; exercise-only; or intensive dietary restriction-only. The primary aims are to compare the effects of these interventions on inflammatory biomarkers and knee joint loads. Secondary aims will examine the effects of these interventions on function, pain, and mobility; the dose response to weight loss on disease progression; if inflammatory biomarkers and knee joint loads are mediators of the interventions; and the association between quadriceps strength and disease progression. Results Test-retest reliability results indicated that the ICCs for knee joint load variables were excellent, ranging from 0.86 – 0.98. Knee flexion/extension moments were most affected by BMI, with lower reliability with the highest tertile of BMI. The reliability of the semi-quantitative scoring of the knee joint using MRI exceeded previously reported results, ranging from a low of 0.66 for synovitis to a high of 0.99 for bone marrow lesion size. Discussion The IDEA trial has the potential to enhance our understanding of the OA disease process, refine weight loss and exercise recommendations in this prevalent disease, and reduce the burden of disability. Trial Registration NCT00381290
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- 2009
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24. Genetic variants in FGFR2 and FGFR4 genes and skin cancer risk in the Nurses' Health Study
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Qureshi Abrar A, Nan Hongmei, Hunter David J, and Han Jiali
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The human fibroblast growth factor (FGF) and its receptor (FGFR) play an important role in tumorigenesis. Deregulation of the FGFR2 gene has been identified in a number of cancer sites. Overexpression of the FGFR4 protein has been linked to cutaneous melanoma progression. Previous studies reported associations between genetic variants in the FGFR2 and FGFR4 genes and development of various cancers. Methods We evaluated the associations of four genetic variants in the FGFR2 gene highly related to breast cancer risk and the three common tag-SNPs in the FGFR4 gene with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 controls. Results We found no evidence for associations between these seven genetic variants and the risks of melanoma and nonmelanocytic skin cancer. Conclusion Given the power of this study, we did not detect any contribution of genetic variants in the FGFR2 or FGFR4 genes to inherited predisposition to skin cancer among Caucasian women.
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- 2009
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25. Identification of two novel activities of the Wnt signaling regulator Dickkopf 3 and characterization of its expression in the mouse retina
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Yi Hyun, Hunter Dale D, Nakamura Rei EI, Brunken William J, and Hackam Abigail S
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Cytology ,QH573-671 - Abstract
Abstract Background The Wnt signaling pathway is a cellular communication pathway that plays critical roles in development and disease. A major class of Wnt signaling regulators is the Dickkopf (Dkk) family of secreted glycoproteins. Although the biological properties of Dickkopf 1 (Dkk1) and Dickkopf 2 (Dkk2) are well characterized, little is known about the function of the related Dickkopf 3 (Dkk3) protein in vivo or in cell lines. We recently demonstrated that Dkk3 transcripts are upregulated during photoreceptor death in a mouse model of retinal degeneration. In this study, we characterized the activity of Dkk3 in Wnt signaling and cell death. Results Dkk3 was localized to Müller glia and retinal ganglion cells in developing and adult mouse retina. Western blotting confirmed that Dkk3 is secreted from Müller glia cells in culture. We demonstrated that Dkk3 potentiated Wnt signaling in Müller glia and HEK293 cells but not in COS7 cells, indicating that it is a cell-type specific regulator of Wnt signaling. This unique Dkk3 activity was blocked by co-expression of Dkk1. Additionally, Dkk3 displayed pro-survival properties by decreasing caspase activation and increasing viability in HEK293 cells exposed to staurosporine and H2O2. In contrast, Dkk3 did not protect COS7 cells from apoptosis. Conclusion These data demonstrate that Dkk3 is a positive regulator of Wnt signaling, in contrast to its family member Dkk1. Furthermore, Dkk3 protects against apoptosis by reducing caspase activity, suggesting that Dkk3 may play a cytoprotective role in the retina.
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- 2007
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26. The effects of hip muscle strengthening on knee load, pain, and function in people with knee osteoarthritis: a protocol for a randomised, single-blind controlled trial
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Hunter David J, Wrigley Tim V, Hunt Michael A, Bennell Kim L, and Hinman Rana S
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Lower limb strengthening exercises are an important component of the treatment for knee osteoarthritis (OA). Strengthening the hip abductor and adductor muscles may influence joint loading and/or OA-related symptoms, but no study has evaluated these hypotheses directly. The aim of this randomised, single-blind controlled trial is to determine whether hip abductor and adductor muscle strengthening can reduce knee load and improve pain and physical function in people with medial compartment knee OA. Methods/Design 88 participants with painful, radiographically confirmed medial compartment knee OA and varus alignment will be recruited from the community and randomly allocated to a hip strengthening or control group using concealed allocation stratified by disease severity. The hip strengthening group will perform 6 exercises to strengthen the hip abductor and adductor muscles at home 5 times per week for 12 weeks. They will consult with a physiotherapist on 7 occasions to be taught the exercises and progress exercise resistance. The control group will be requested to continue with their usual care. Blinded follow up assessment will be conducted at 12 weeks after randomisation. The primary outcome measure is the change in the peak external knee adduction moment measured during walking. Questionnaires will assess changes in pain and physical function as well as overall perceived rating of change. An intention-to-treat analysis will be performed using linear regression modelling and adjusting for baseline outcome values and other demographic characteristics. Discussion Results from this trial will contribute to the evidence regarding the effect of hip strengthening on knee loads and symptoms in people with medial compartment knee OA. If shown to reduce the knee adduction moment, hip strengthening has the potential to slow disease progression. Trial Registration Australia New Zealand Clinical Trials Registry ACTR12607000001493
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- 2007
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27. TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study
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Guo Qun, Penney Kathryn, Cox David G, Hankinson Susan E, and Hunter David J
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Transforming growth factor beta 1 (TGFB1) forms a signaling complex with transforming growth factor beta receptors 1 and 2 and has been described as both a tumor suppressor and tumor promoter. Single nucleotide polymorphisms in TGFB1 and a microsatellite in TGFBR1 have been investigated for association with risk of breast cancer, with conflicting results. Methods We examined polymorphisms in the promoter region of the TGFB1 gene as well as the TGFBR1*6A microsatellite in the Nurses' Health Study cohort. Results No overall associations between the L10P polymorphism of TGFB1 or the TGFBR1 microsatellite were detected. However, we observed an inverse association between the -509 C/T polymorphism of TGFB1 (p-trend = 0.04), which was stronger and more significant among women with estrogen receptor positive breast cancer. Conclusion Polymorphisms in the promoter region of TGFB1 are not likely to be associated with large increases in breast cancer risk overall among Caucasian women.
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- 2007
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28. Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1
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Gutowski Nicholas J, Pott Jan WR, Traboulsi Elias I, Yazdani Ahmad, Hunter David G, Geraghty Michael T, Lyons Christopher, Armstrong Linlea, Fredrick Douglas, Dragan Laryssa, Andrews Caroline, Chan Wai-Man, Ellard Sian, Young Elizabeth, Hanisch Frank, Koc Feray, Schnall Bruce, and Engle Elizabeth C
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Genetics ,QH426-470 - Abstract
Abstract Background Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A. Results Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands. Conclusion Analysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.
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- 2007
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29. Gene × Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study
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Tamimi Rulla M, Cox David G, and Hunter David J
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. Methods A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. Results While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 – 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. Conclusion Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer.
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- 2006
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30. A Study of Two Dwarf Irregular Galaxies with Asymmetrical Star Formation Distributions
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Stacey N. Bright, Robert C. Kennicutt, Angela Adamo, David O. Cook, Deidre A. Hunter, Bruce G. Elmegreen, Michele Fumagalli, Elena Sabbi, Matteo Messa, Lauren Kahre, J. E. Ryon, Elena Sacchi, L. Ubeda, John S. Gallagher, Se-Heon Oh, Hong-Xin Zhang, Eva K. Grebel, Monica Tosi, Daniel A. Dale, Hwihyun Kim, Kathryn Grasha, Dimitrios A. Gouliermis, Samavarti Gallardo, Michele Cignoni, Daniela Calzetti, Janice C. Lee, Hunter, D, Gallardo, S, Zhang, H, Adamo, A, Cook, D, Oh, S, Elmegreen, B, Kim, H, Kahre, L, Ubeda, L, Bright, S, Ryon, J, Fumagalli, M, Sacchi, E, Kennicutt, R, Tosi, M, Dale, D, Cignoni, M, Messa, M, Grebel, E, Gouliermis, D, Sabbi, E, Grasha, K, Gallagher, J, Calzetti, D, Lee, J, Hunter, DA [0000-0002-3322-9798], Adamo, A [0000-0002-8192-8091], Cook, DO [0000-0002-6877-7655], Oh, SH [0000-0002-5648-9920], Elmegreen, BG [0000-0002-1723-6330], Kim, H [0000-0003-4770-688X], Kahre, L [0000-0002-2037-3096], Fumagalli, M [0000-0001-6676-3842], Sacchi, E [0000-0001-5618-0109], Tosi, M [0000-0002-0986-4759], Dale, DA [0000-0002-5782-9093], Cignoni, M [0000-0001-6291-6813], Grebel, EK [0000-0002-1891-3794], Gouliermis, DA [0000-0002-2763-0075], Sabbi, E [0000-0003-2954-7643], Grasha, K [0000-0002-3247-5321], Gallagher, JS [0000-0001-8608-0408], Calzetti, D [0000-0002-5189-8004], Lee, JC [0000-0002-2278-9407], and Apollo - University of Cambridge Repository
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010504 meteorology & atmospheric sciences ,FOS: Physical sciences ,galaxies: individual (DDO 187, NGC 3738) ,Astrophysics ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Rotation ,01 natural sciences ,0103 physical sciences ,Dispersion (optics) ,Astrophysics::Solar and Stellar Astrophysics ,010303 astronomy & astrophysics ,Astrophysics::Galaxy Astrophysics ,0105 earth and related environmental sciences ,Physics ,NGC 3738) ,Star formation ,Astronomy and Astrophysics ,galaxies: dwarf ,galaxies: individual (DDO 187 ,Astrophysics - Astrophysics of Galaxies ,Galaxy ,Space and Planetary Science ,Astrophysics of Galaxies (astro-ph.GA) ,galaxies: star formation ,Irregular galaxy - Abstract
Two dwarf irregular galaxies DDO 187 and NGC 3738 exhibit a striking pattern of star formation: intense star formation is taking place in a large region occupying roughly half of the inner part of the optical galaxy. We use data on the HI distribution and kinematics and stellar images and colors to examine the properties of the environment in the high star formation rate (HSF) halves of the galaxies in comparison with the low star formation rate (LSF) halves. We find that the pressure and gas density are higher on the HSF sides by 30-70%. In addition we find in both galaxies that the HI velocity fields exhibit significant deviations from ordered rotation and there are large regions of high velocity dispersion and multiple velocity components in the gas beyond the inner regions of the galaxies. The conditions in the HSF regions are likely the result of large-scale external processes affecting the internal environment of the galaxies and enabling the current star formation there., Comment: In press in ApJ
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- 2018
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31. The Resolved Stellar Populations in the LEGUS Galaxies1
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D. M. Elmegreen, Elena Sabbi, A. Dolphin, Geoffrey C. Clayton, Eva K. Grebel, Linda J. Smith, T. M. Brown, G. Ashworth, R. Walterbos, Matteo Messa, Lauren Kahre, J. Prieto, Alessandra Aloisi, Rupali Chandar, C. D. Martin, Mark R. Krumholz, M. W. Regan, Daniel A. Dale, Bruce G. Elmegreen, Hwihyun Kim, Kathryn Grasha, Elena Sacchi, F. Shabani, A. Herrero, R. C. Kennicutt, David O. Cook, J. E. Ryon, A. Nota, B. C. Whitmore, L. Ubeda, D. Schaerer, D. Schiminovich, Jennifer E. Andrews, J. C. Lee, Stacey N. Bright, Dimitrios A. Gouliermis, John S. Gallagher, D. J. Lennon, Michele Fumagalli, Daniela Calzetti, Kelsey E. Johnson, Michele Cignoni, S. D. Van Dyk, C. Christian, P. Nair, Clare Dobbs, Aaron S. Evans, Monica Tosi, G. Ostlin, Anne Pellerin, Deidre A. Hunter, David A. Thilker, Angela Adamo, S. E. de Mink, Aida Wofford, Sabbi, E, Calzetti, D, Ubeda, L, Adamo, A, Cignoni, M, Thilker, D, Aloisi, A, Elmegreen, B, Elmegreen, D, Gouliermis, D, Grebel, E, Messa, M, Smith, L, Tosi, M, Dolphin, A, Andrews, J, Ashworth, G, Bright, S, Brown, T, Chandar, R, Christian, C, Clayton, G, Cook, D, Dale, D, De Mink, S, Dobbs, C, Evans, A, Fumagalli, M, Gallagher, J, Grasha, K, Herrero, A, Hunter, D, Johnson, K, Kahre, L, Kennicutt, R, Kim, H, Krumholz, M, Lee, J, Lennon, D, Martin, C, Nair, P, Nota, A, Ostlin, G, Pellerin, A, Prieto, J, Regan, M, Ryon, J, Sacchi, E, Schaerer, D, Schiminovich, D, Shabani, F, Van Dyk, S, Walterbos, R, Whitmore, B, Wofford, A, Sabbi, E [0000-0003-2954-7643], Calzetti, D [0000-0002-5189-8004], Adamo, A [0000-0002-8192-8091], Cignoni, M [0000-0001-6291-6813], Thilker, D [0000-0002-8528-7340], Aloisi, A [0000-0003-4137-882X], Elmegreen, BG [0000-0002-1723-6330], Elmegreen, DM [0000-0002-1392-3520], Gouliermis, DA [0000-0002-2763-0075], Grebel, EK [0000-0002-1891-3794], Smith, LJ [0000-0002-0806-168X], Tosi, M [0000-0002-0986-4759], Dolphin, A [0000-0001-8416-4093], Chandar, R [0000-0003-0085-4623], Clayton, GC [0000-0002-0141-7436], Dale, DA [0000-0002-5782-9093], Grasha, K [0000-0002-3247-5321], Hunter, DA [0000-0002-3322-9798], Johnson, KE [0000-0001-8348-2671], Kahre, L [0000-0002-2037-3096], Pellerin, A [0000-0003-1887-1966], Prieto, J [0000-0003-0943-0026], Sacchi, E [0000-0001-5618-0109], Schaerer, D [0000-0001-7144-7182], Shabani, F [0000-0002-5266-1260], Walterbos, R [0000-0002-0782-3064], Apollo - University of Cambridge Repository, and Low Energy Astrophysics (API, FNWI)
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Hertzsprung–Russell diagram ,Russell and C-M diagram ,Astrophysics ,Astrophysics::Cosmology and Extragalactic Astrophysics ,01 natural sciences ,Advanced Camera for Surveys ,symbols.namesake ,galaxies: star clusters: general ,galaxies: star formation ,galaxies: stellar content ,Hertzsprung ,Russell and C-M diagrams ,stars: formation ,Astronomy and Astrophysics ,Space and Planetary Science ,0103 physical sciences ,Astrophysics::Solar and Stellar Astrophysics ,010303 astronomy & astrophysics ,Astrophysics::Galaxy Astrophysics ,Physics ,010308 nuclear & particles physics ,Star formation ,Galaxy ,Red-giant branch ,Stars ,Star cluster ,symbols ,Hertzsprung-Russell and C-M diagrams ,Astrophysics::Earth and Planetary Astrophysics ,Wide Field Camera 3 - Abstract
The Legacy ExtraGalactic UV Survey (LEGUS) is a multiwavelength Cycle 21 Treasury program on the Hubble Space Telescope. It studied 50 nearby star-forming galaxies in 5 bands from the near-UV to the I-band, combining new Wide Field Camera 3 observations with archival Advanced Camera for Surveys data. LEGUS was designed to investigate how star formation occurs and develops on both small and large scales, and how it relates to the galactic environments. In this paper we present the photometric catalogs for all the apparently single stars identified in the 50 LEGUS galaxies. Photometric catalogs and mosaicked images for all filters are available for download. We present optical and near-UV color-magnitude diagrams for all the galaxies. For each galaxy we derived the distance from the tip of the red giant branch. We then used the NUV color-magnitude diagrams to identify stars more massive than 14 M ☉, and compared their number with the number of massive stars expected from the GALEX FUV luminosity. Our analysis shows that the fraction of massive stars forming in star clusters and stellar associations is about constant with the star formation rate. This lack of a relation suggests that the timescale for evaporation of unbound structures is comparable or longer than 10 Myr. At low star formation rates this translates to an excess of mass in clustered environments as compared to model predictions of cluster evolution, suggesting that a significant fraction of stars form in unbound systems. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA Inc., under NASA contract NAS 5-26555.
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- 2018
32. Extinction Maps and Dust-to-gas Ratios in Nearby Galaxies with LEGUS
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Leonardo Ubeda, Aaron S. Evans, Debra Meloy Elmegreen, Brad Whitmore, Daniel A. Dale, Janice C. Lee, Rene A. M. Walterbos, Carol Christian, Linda J. Smith, Rupali Chandar, Hwihyun Kim, R. C. Kennicutt, F. Shabani, Kathryn Grasha, Clare Dobbs, Dimitrios A. Gouliermis, Jennifer E. Andrews, Bruce G. Elmegreen, Alessandra Aloisi, Daniela Calzetti, J. E. Ryon, Michele Cignoni, Aida Wofford, Deidre A. Hunter, Michele Fumagalli, S. E. de Mink, John S. Gallagher, Elena Sabbi, David A. Thilker, Stacey N. Bright, Daniel Schaerer, S. D. Van Dyk, Preethi Nair, Kelsey E. Johnson, Matteo Messa, Antonella Nota, A. Herrero, Mark R. Krumholz, Elena Sacchi, Thomas M. Brown, Angela Adamo, L. Kahre, G. Ashworth, Eva K. Grebel, Monica Tosi, David O. Cook, Anne Pellerin, Low Energy Astrophysics (API, FNWI), Kahre, L [0000-0002-2037-3096], Walterbos, RA [0000-0002-0782-3064], Kim, H [0000-0003-4770-688X], Thilker, D [0000-0002-8528-7340], Calzetti, D [0000-0002-5189-8004], Lee, JC [0000-0002-2278-9407], Sabbi, E [0000-0003-2954-7643], Aloisi, A [0000-0003-4137-882X], Cignoni, M [0000-0001-6291-6813], Cook, DO [0000-0002-6877-7655], Dale, DA [0000-0002-5782-9093], Elmegreen, BG [0000-0002-1723-6330], Elmegreen, DM [0000-0002-1392-3520], Fumagalli, M [0000-0001-6676-3842], Gallagher, JS [0000-0001-8608-0408], Gouliermis, DA [0000-0002-2763-0075], Grasha, K [0000-0002-3247-5321], Grebel, EK [0000-0002-1891-3794], Hunter, DA [0000-0002-3322-9798], Sacchi, E [0000-0001-5618-0109], Smith, LJ [0000-0002-0806-168X], Tosi, M [0000-0002-0986-4759], Adamo, A [0000-0002-8192-8091], Brown, TM [0000-0002-1793-9968], Chandar, R [0000-0003-0085-4623], Christian, C [0000-0002-2179-3308], De Mink, SE [0000-0001-9336-2825], Herrero, A [0000-0001-8768-2179], Johnson, KE [0000-0001-8348-2671], Krumholz, MR [0000-0003-3893-854X], Pellerin, A [0000-0003-1887-1966], Schaerer, D [0000-0001-7144-7182], Shabani, F [0000-0002-5266-1260], Van Dyk, SD [0000-0001-9038-9950], Apollo - University of Cambridge Repository, Kahre, L, Walterbos, R, Kim, H, Thilker, D, Calzetti, D, Lee, J, Sabbi, E, Ubeda, L, Aloisi, A, Cignoni, M, Cook, D, Dale, D, Elmegreen, B, Elmegreen, D, Fumagalli, M, Gallagher, J, Gouliermis, D, Grasha, K, Grebel, E, Hunter, D, Sacchi, E, Smith, L, Tosi, M, Adamo, A, Andrews, J, Ashworth, G, Bright, S, Brown, T, Chandar, R, Christian, C, De Mink, S, Dobbs, C, Evans, A, Herrero, A, Johnson, K, Kennicutt, R, Krumholz, M, Messa, M, Nair, P, Nota, A, Pellerin, A, Ryon, J, Schaerer, D, Shabani, F, Van Dyk, S, Whitmore, B, and Wofford, A
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galaxies: spiral ,Metallicity ,FOS: Physical sciences ,Astrophysics ,Astrophysics::Cosmology and Extragalactic Astrophysics ,01 natural sciences ,Power law ,Hubble space telescope ,0103 physical sciences ,Astrophysics::Solar and Stellar Astrophysics ,010303 astronomy & astrophysics ,Astrophysics::Galaxy Astrophysics ,ISM: general ,Physics ,Extinction ,010308 nuclear & particles physics ,extinction ,Astronomy and Astrophysics ,HERA ,galaxies: dwarf ,Astrophysics - Astrophysics of Galaxies ,Galaxy ,Stars ,dust ,galaxies: ISM ,galaxies: photometry ,Space and Planetary Science ,Astrophysics of Galaxies (astro-ph.GA) ,Spectral energy distribution ,dust, extinction ,Astrophysics::Earth and Planetary Astrophysics - Abstract
We present a study of the dust-to-gas ratios in five nearby galaxies NGC 628 (M74), NGC 6503, NGC 7793, UGC 5139 (Holmberg I), and UGC 4305 (Holmberg II). Using Hubble Space Telescope broad band WFC3/UVIS UV and optical images from the Treasury program LEGUS (Legacy ExtraGalactic UV Survey) combined with archival HST/ACS data, we correct thousands of individual stars for extinction across these five galaxies using an isochrone-matching (reddening-free Q) method. We generate extinction maps for each galaxy from the individual stellar extinctions using both adaptive and fixed resolution techniques, and correlate these maps with neutral HI and CO gas maps from literature, including The HI Nearby Galaxy Survey (THINGS) and the HERA CO-Line Extragalactic Survey (HERACLES). We calculate dust-to-gas ratios and investigate variations in the dust-to-gas ratio with galaxy metallicity. We find a power law relationship between dust-to-gas ratio and metallicity, consistent with other studies of dust-to-gas ratio compared to metallicity. We find a change in the relation when H$_2$ is not included. This implies that underestimation of $N_{H_2}$ in low-metallicity dwarfs from a too-low CO-to-H$_2$ conversion factor $X_{CO}$ could have produced too low a slope in the derived relationship between dust-to-gas ratio and metallicity. We also compare our extinctions to those derived from fitting the spectral energy distribution (SED) using the Bayesian Extinction and Stellar Tool (BEAST) for NGC 7793 and find systematically lower extinctions from SED-fitting as compared to isochrone matching., Comment: 22 pages, 14 figures, accepted by ApJ
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- 2018
33. SmuMYB113 is the determinant of fruit color in pepino ( Solanum muricatum ).
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Martinez-Sanchez M, Hunter DA, Saei A, Andre CM, Varkonyi-Gasic E, Clark G, Barry E, and Allan AC
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Pepino ( Solanum muricatum ) is an herbaceous crop phylogenetically related to tomato and potato. Pepino fruit vary in color, size and shape, and are eaten fresh. In this study, we use pepino as a fruit model to understand the transcriptional regulatory mechanisms controlling fruit quality. To identify the key genes involved in anthocyanin biosynthesis in pepino, two genotypes were studied that contrasted in foliar and fruit pigmentation. Anthocyanin profiles were analyzed, as well as the expression of genes that encode enzymes for anthocyanin biosynthesis and transcriptional regulators using both RNA-seq and quantitative PCR. The differential expression of the transcription factor genes R2R3 MYB SmuMYB113 and R3MYB SmuATV suggested their association with purple skin and foliage phenotype. Functional analysis of these genes in both tobacco and pepino showed that SmuMYB113 activates anthocyanins, while SmuATV suppresses anthocyanin accumulation. However, despite elevated expression in all tissues, SmuMYB113 does not significantly elevate flesh pigmentation, suggesting a strong repressive background in fruit flesh tissue. These results will aid understanding of the differential regulation controlling fruit quality aspects between skin and flesh in other fruiting species., Competing Interests: Authors MM-S and AA are employed by Plant & Food Research and the University of Auckland. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martinez-Sanchez, Hunter, Saei, Andre, Varkonyi-Gasic, Clark, Barry and Allan.)
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- 2024
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34. Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.
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Acevedo Cintrón JA, Hunter DA, Schellhardt L, Pan D, Mackinnon SE, and Wood MD
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- Animals, Rats, Axons metabolism, Male, Blood Vessels, Inflammation pathology, Inflammation metabolism, Cellular Microenvironment, Transplantation, Homologous, Cytokines metabolism, Rats, Sprague-Dawley, Nerve Regeneration, Sciatic Nerve, Allografts
- Abstract
The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.
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- 2024
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35. Effect of Veau Class on Levator Veli Palatini Muscle Composition.
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Chiang SN, Meyer GA, Skolnick GB, Hunter DA, Wood MD, Li X, Snyder-Warwick AK, and Patel KB
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- Humans, Prospective Studies, Palate, Soft, Palatal Muscles, Collagen, Cleft Palate surgery
- Abstract
Objective: To examine levator veli palatini muscle composition in patients with nonsyndromic cleft palate and investigate the impact of Veau class., Design: Prospective cohort study., Setting: Tertiary care academic hospital., Patients/participants: Thirteen patients with nonsyndromic cleft palate were recruited., Interventions: During primary palatoplasty, a sample of levator veli palatini muscle was excised and prepared for histological analysis., Main Outcome Measures: Fat and collagen content were determined utilizing Oil Red and Sirius red stains, respectively, while muscle fiber cross-sectional areas were calculated from H&E-stained samples, with analysis using histomorphometric methods. Immunofluorescent staining of myosin heavy chain isoforms was performed., Results: Patients underwent repair at 10.8 months of age (interquartile range [IQR] 10.2-12.9). Fat content of the levator veli palatini muscle was low in both groups, ranging from 0% to 5.2%. Collagen content ranged from 8.5% to 39.8%; neither fat nor collagen content showed an association with Veau classes. Mean muscle fiber cross-sectional area decreased with increasing Veau class, from 808 µm
2 (range 692-995 µm2 ) in Veau II to 651 µm2 (range 232-750 µm2 ) in Veau III ( P = .02). There was also a nonsignificant decrease in proportion of type I muscle fibers with increasing Veau class (44.3% [range 31.4%-84.4%] in Veau II vs 35.3% [range 17.4%-61.3%] in Veau III)., Conclusions: Muscle fiber area in levator veli palatini muscles decreases in Veau III clefts in comparison to Veau II. The impact of these differences in velopharyngeal dysfunction requires further analysis of a larger cohort., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KBP is a consultant for Stryker CMF.- Published
- 2024
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36. A Rare and Unique Complication of Uncontrolled Type 2 Diabetes Mellitus: A Case Report and Literature Review of Spontaneous Diabetic Myonecrosis.
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Johnson AM, Oo ZT, Oo TS, Hunter DA, Htet ZM, Bejugam VR, and Purice G
- Abstract
There are many microvascular and macrovascular complications regarding uncontrolled diabetes mellitus (DM). Among them, diabetes myonecrosis is one of the complications but rarely seen in the uncontrolled DM patient population. Here, we present a rare case of DM myonecrosis in a patient with elevated hemoglobin A1c (HbA1c) of 18.2% and discuss the literature review of diabetes myonecrosis. A 48-year-old male with hypertension and uncontrolled type 2 diabetes mellitus (T2DM) with hemoglobin A1c of 18.2% presented with progressive swelling and pain in the right thigh for two days. Physical examination demonstrated swollen and tense tender right thigh with a circumference five inches larger than the left. Computed tomography (CT) and magnetic resonance imaging (MRI) results revealed severe myositis of the right leg, likely myonecrosis, and associated fascial edema/fasciitis. The patient was also complicated with diffuse anasarca, which was corrected with albumin transfusion and furosemide. Aspirin and lisinopril were also started for antithrombotic and cardioprotective effects. The right thigh swelling improved, and the patient could ambulate with supportive measures and regular physical therapy (PT). He was discharged home after 45 days of hospitalization. Diabetic myonecrosis is a rare condition and hence is underdiagnosed. In patients with uncontrolled diabetes, especially with diabetic complications, physicians should have high clinical suspicion to diagnose diabetic myonecrosis when patients present with an acute unilateral painful swollen limb. Our case highlights the complicated course of diabetes myonecrosis with anasarca, improved with supportive measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Johnson et al.)
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- 2023
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37. Acellular Nerve Allografts in Major Peripheral Nerve Repairs: An Analysis of Cases Presenting With Limited Recovery.
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Peters BR, Wood MD, Hunter DA, and Mackinnon SE
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- Humans, Allografts, Nerve Regeneration physiology, Transplantation, Homologous, Peripheral Nerves surgery, Peripheral Nerve Injuries surgery
- Abstract
Background: Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts., Methods: Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination., Results: Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft., Conclusions: The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered.
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- 2023
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38. Lidocaine Nerve Block Diminishes the Effects of Therapeutic Electrical Stimulation to Enhance Nerve Regeneration in Rats.
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Keane GC, Marsh EB, Hunter DA, Schellhardt L, Walker ER, and Wood MD
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- Animals, Rats, Axons physiology, Nerve Regeneration physiology, Electric Stimulation Therapy, Lidocaine pharmacology
- Abstract
Background: Although electrical stimulation (ES) can improve nerve regeneration, the impact of nerve block, such as lidocaine (Lido), on the therapeutic benefits of ES remains unclear. We used a rat tibial nerve transection-and-repair model to explore how either preoperative (PreOp) or postoperative (PostOp) nerve block affects ES-related improvement in regeneration., Methods: Lewis rats were used in 1 of 2 studies. The first evaluated the effects of extraneural Lido on both healthy and injured nerves. In the second study, rats were randomized to 5 experimental groups: No ES (negative control), PreOp Lido, ES + PreOp Lido, PostOp + ES, and ES (positive control). All groups underwent tibial nerve transection and repair. In both studies, nerves were harvested for histological analysis of regeneration distal to the injury site., Results: Application of extraneural Lido did not damage healthy or injured nerve based on qualitative histological observations. In the context of nerve transection and repair, the ES group exhibited improved axon regeneration at 21 days measured by the total number of myelinated fibers compared with No ES. Fiber density and percentage of neural tissue in the ES group were greater than those in both No ES and PreOp Lido + ES groups. ES + PostOp Lido was not different from No ES or ES group., Conclusions: Extraneural application of Lido did not damage nerves. Electrical stimulation augmented nerve regeneration, but Lido diminished the ES-related improvement in nerve regeneration. Clinical studies on the effects of ES to nerve regeneration may need to consider nerve block as a variable affecting ES outcome.
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- 2023
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39. Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes.
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Marsh EB, Schellhardt L, Hunter DA, Mackinnon SE, Snyder-Warwick AK, and Wood MD
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- Animals, Rats, Electric Stimulation, Nerve Regeneration physiology, Recovery of Function physiology, Tibial Nerve pathology, Random Allocation, Immunosuppressive Agents pharmacology, Immunosuppressive Agents therapeutic use, Tacrolimus pharmacology, Tacrolimus therapeutic use
- Abstract
Introduction/aims: Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E-stim), can improve recovery. We tested whether dual administration of FK506 and E-stim enhances regeneration and recovery more than either therapeutic alone., Methods: Rats were randomized to four groups: E-stim, FK506, FK506 + E-stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21- and 42-day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force., Results: Dual E-stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P < .0001; E-stim, P < .05; FK506 + E-stim, P < .05). The E-stim and FK506 + E-stim groups had improved behavioral recovery compared with repair alone (at 6 weeks: E-stim, P < .05; FK506 + E-stim, P < .01). The FK506 group had improved recovery based on walking-track analysis (at 6 weeks: P < .001) and muscle force and mass (P < .05). The concurrent use of both therapies ensured earlier functional recovery and decreased variability in functional outcomes compared with either therapy alone, suggesting a moderate benefit., Discussion: Dual administration of FK506 and E-stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E-stim appears to combine the relative strengths of each therapeutic., (© 2022 Wiley Periodicals LLC.)
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- 2023
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40. Controlling axonal regeneration with acellular nerve allograft limits neuroma formation in peripheral nerve transection: An experimental study in a swine model.
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Grimm PD, Wheatley BM, Tomasino A, Leonhardt C, Hunter DA, Wood MD, Moore AM, Davis TA, and Tintle SM
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- Allografts pathology, Animals, Axons physiology, Female, Nerve Regeneration physiology, Sciatic Nerve surgery, Swine, Nerve Tissue pathology, Neuroma etiology, Neuroma prevention & control, Neuroma surgery
- Abstract
Background: Symptomatic neuromata are a common indication for revision surgery following amputation. Previously described treatments, including traction neurectomy, nerve transposition, targeted muscle re-innervation, and nerve capping, have provided inconsistent results or are technically challenging. Prior research using acellular nerve allografts (ANA) has shown controlled termination of axonal regrowth in long grafts. The purpose of this study was to determine the ability of a long ANA to prevent neuroma formation following transection of a peripheral nerve in a swine model., Materials and Methods: Twenty-two adult female Yucatan miniature swine (Sus scrofa; 4-6 months, 15-25 kg) were assigned to control (ulnar nerve transection only, n = 10), treatment (ulnar transection and coaptation of 50 mm ANA, n = 10), or donor (n = 2) groups. Nerves harvested from donor group animals were treated to create the ANA. After 20 weeks, the transected nerves including any neuroma or graft were harvested. Both qualitative (nerve architecture, axonal sprouting) and quantitative histologic analyses (myelinated axon number, cross sectional area of nerve tissue) were performed., Results: Qualitative histologic analysis of control specimens revealed robust axon growth into dense scar tissue. In contrast, the treatment group revealed dwindling axons in the terminal tissue, consistent with attenuated neuroma formation. Quantitative analysis revealed a significantly decreased number of myelinated axons in the treatment group (1232 ± 540) compared to the control group (44,380 ± 7204) (p < .0001). Cross sectional area of nerve tissue was significantly smaller in treatment group (2.83 ± 1.53 mm
2 ) compared to the control group (9.14 ± 1.19 mm2 ) (p = .0012)., Conclusions: Aberrant axonal growth is controlled to termination with coaptation of a 50 mm ANA in a swine model of nerve injury. These early results suggest further investigation of this technique to prevent and/or treat neuroma formation., (© 2022 Wiley Periodicals LLC.)- Published
- 2022
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41. Assessing the Impact of Secondary Fluorescence on X-Ray Microanalysis Results from Semiconductor Thin Films.
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Hunter DA, Lavery SP, Edwards PR, and Martin RW
- Abstract
The impact of secondary fluorescence on the material compositions measured by X-ray analysis for layered semiconductor thin films is assessed using simulations performed by the DTSA-II and CalcZAF software tools. Three technologically important examples are investigated: AlxGa1−xN layers on either GaN or AlN substrates, InxAl1−xN on GaN, and Si-doped (SnxGa1−x)2O3 on Si. Trends in the differences caused by secondary fluorescence are explained in terms of the propensity of different elements to reabsorb either characteristic or bremsstrahlung X-rays and then to re-emit the characteristic X-rays used to determine composition of the layer under investigation. Under typical beam conditions (7–12 keV), the quantification of dopants/trace elements is found to be susceptible to secondary fluorescence and care must be taken to prevent erroneous results. The overall impact on major constituents is shown to be very small with a change of approximately 0.07 molar cation percent for Al0.3Ga0.7N/AlN layers and a maximum change of 0.08 at% in the Si content of (SnxGa1−x)2O3/Si layers. This provides confidence that previously reported wavelength-dispersive X-ray compositions are not compromised by secondary fluorescence.
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- 2022
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42. Eradication of Potato Virus S , Potato Virus A , and Potato Virus M From Infected in vitro -Grown Potato Shoots Using in vitro Therapies.
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Bettoni JC, Mathew L, Pathirana R, Wiedow C, Hunter DA, McLachlan A, Khan S, Tang J, and Nadarajan J
- Abstract
Certain viruses dramatically affect yield and quality of potatoes and have proved difficult to eradicate with current approaches. Here, we describe a reliable and efficient virus eradication method that is high throughput and more efficacious at producing virus-free potato plants than current reported methods. Thermotherapy, chemotherapy, and cryotherapy treatments were tested alone and in combination for ability to eradicate single and mixed Potato virus S (PVS), Potato virus A (PVA), and Potato virus M (PVM) infections from three potato cultivars. Chemotherapy treatments were undertaken on in vitro shoot segments for four weeks in culture medium supplemented with 100 mg L
-1 ribavirin. Thermotherapy on in vitro shoot segments was applied for two weeks at 40°C (day) and 28°C (night) with a 16 h photoperiod. Plant vitrification solution 2 (PVS2) and cryotherapy treatments included a shoot tip preculture followed by exposure to PVS2 either without or with liquid nitrogen (LN, cryotherapy) treatment. The virus status of control and recovered plants following therapies was assessed in post-regeneration culture after 3 months and then retested in plants after they had been growing in a greenhouse for a further 3 months. Microtuber production was investigated using in vitro virus-free and virus-infected segments. We found that thermotherapy and cryotherapy (60 min PVS2 + LN) used alone were not effective in virus eradication, while chemotherapy was better but with variable efficacy (20-100%). The most effective result (70-100% virus eradication) was obtained by combining chemotherapy with cryotherapy, or by consecutive chemotherapy, combined chemotherapy and thermotherapy, then cryotherapy treatments irrespective of cultivar. Regrowth following the two best virus eradication treatments was similar ranging from 8.6 to 29% across the three cultivars. The importance of virus removal on yield was reflected in "Dunluce" free of PVS having higher numbers of microtubers and in "V500' free of PVS and PVA having a greater proportion of microtubers > 5 mm. Our improved procedure has potential for producing virus-free planting material for the potato industry. It could also underpin the global exchange of virus-free germplasm for conservation and breeding programs., Competing Interests: JB LM, RP, CW, DH, AM, and JN were employed by The New Zealand Institute for Plant and Food Research Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bettoni, Mathew, Pathirana, Wiedow, Hunter, McLachlan, Khan, Tang and Nadarajan.)- Published
- 2022
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43. The Effects of Intraoperative Electrical Stimulation on Regeneration and Recovery After Nerve Isograft Repair in a Rat Model.
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Keane GC, Pan D, Roh J, Larson EL, Schellhardt L, Hunter DA, Snyder-Warwick AK, Moore AM, Mackinnon SE, and Wood MD
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- Animals, Electric Stimulation, Humans, Isografts, Rats, Recovery of Function physiology, Axons physiology, Nerve Regeneration physiology
- Abstract
Background: Therapeutic electrical stimulation (ES) applied to repaired nerve is a promising treatment option to improve regeneration. However, few studies address the impact of ES following nerve graft reconstruction. The purpose of this study was to determine if ES applied to a nerve repair using nerve isograft in a rodent model could improve nerve regeneration and functional recovery. Methods: Adult rats were randomized to 2 groups: "ES" and "Control." Rats received a tibial nerve transection that was repaired using a tibial nerve isograft (1.0 cm length), where ES was applied immediately after repair in the applicable group. Nerve was harvested 2 weeks postrepair for immunohistochemical analysis of axon growth and macrophage accumulation. Independently, rats were assessed using walking track and grid-walk analysis for up to 21 weeks. Results: At 2 weeks, more robust axon regeneration and greater macrophage accumulation was observed within the isografts for the ES compared to Control groups. Both walking track and grid-walk analysis revealed that return of functional recovery was accelerated by ES. The ES group demonstrated improved functional recovery over time, as well as improved recovery compared to the Control group at 21 weeks. Conclusions: ES improved early axon regeneration into a nerve isograft and was associated with increased macrophage and beneficial M2 macrophage accumulation within the isograft. ES ultimately improved functional recovery compared to isograft repair alone. This study supports the clinical potential of ES to improve the management of nerve injuries requiring a nerve graft repair.
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- 2022
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44. Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats.
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Roh J, Schellhardt L, Keane GC, Hunter DA, Moore AM, Snyder-Warwick AK, Mackinnon SE, and Wood MD
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- Animals, Humans, Rats, Electric Stimulation methods, Nerve Regeneration physiology, Rats, Inbred Lew, Recovery of Function physiology, Tibial Nerve injuries, Axons physiology, Electric Stimulation Therapy
- Abstract
Background: Repair of nerve injuries can fail to achieve adequate functional recovery. Electrical stimulation applied at the time of nerve repair can accelerate axon regeneration, which may improve the likelihood of recovery. However, widespread use of electrical stimulation may be limited by treatment protocols that increase operative time and complexity. This study evaluated whether a short-duration electrical stimulation protocol (10 minutes) was efficacious to enhance regeneration following nerve repair using rat models., Methods: Lewis and Thy1-green fluorescent protein rats were randomized to three groups: 0 minutes of electrical stimulation (no electrical stimulation; control), 10 minutes of electrical stimulation, and 60 minutes of electrical stimulation. All groups underwent tibial nerve transection and repair. In the intervention groups, electrical stimulation was delivered after nerve repair. Outcomes were assessed using immunohistochemistry, histology, and serial walking track analysis., Results: Two weeks after nerve repair, Thy1-green fluorescent protein rats demonstrated increased green fluorescent protein-positive axon outgrowth from the repair site with electrical stimulation compared to no electrical stimulation. Serial measurement of walking tracks after nerve repair revealed recovery was achieved more rapidly in both electrical stimulation groups as compared to no electrical stimulation. Histologic analysis of nerve distal to the repair at 8 weeks revealed robust axon regeneration in all groups., Conclusions: As little as 10 minutes of intraoperative electrical stimulation therapy increased early axon regeneration and facilitated functional recovery following nerve transection with repair. Also, as early axon outgrowth increased following electrical stimulation with nerve repair, these findings suggest electrical stimulation facilitated recovery because of earlier axon growth across the suture-repaired site into the distal nerve to reach end-organ targets., Clinical Relevance Statement: Brief (10-minute) electrical stimulation therapy can provide similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair rat model and merit further studies, as they represent a translational advantage., Competing Interests: Disclosure:Dr. Wood has been the recipient of sponsored research agreements from Checkpoint Surgical, Inc., and has consulted for AxoGen, Foundry Therapeutics, LLC, and The Foundry, LLC. Checkpoint Surgical did not influence or affect the experimental design or outcome of the studies. No consulting relationship affected the materials in this article. No personal compensation was provided. None of the other authors has any conflicts of interest to disclose., (Copyright © 2022 by the American Society of Plastic Surgeons.)
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- 2022
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45. Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice.
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Sayanagi J, Acevedo-Cintrón JA, Pan D, Schellhardt L, Hunter DA, Snyder-Warwick AK, Mackinnon SE, and Wood MD
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- Animals, Male, Mice, Peripheral Nerve Injuries physiopathology, Recovery of Function physiology, Sciatic Nerve injuries, Axons physiology, Electric Stimulation methods, Nerve Regeneration physiology, Peripheral Nerve Injuries therapy, Sciatic Nerve physiopathology
- Abstract
Background: Clinical outcomes following nerve injury repair can be inadequate. Pulsed-current electrical stimulation (ES) is a therapeutic method that facilitates functional recovery by accelerating axon regeneration. However, current clinical ES protocols involve the application of ES for 60 minutes during surgery, which can increase operative complexity and time. Shorter ES protocols could be a strategy to facilitate broader clinical adoption. The purpose of the present study was to determine if a 10-minute ES protocol could improve outcomes., Methods: C57BL/6J mice were randomized to 3 groups: no ES, 10 minutes of ES, and 60 minutes of ES. In all groups, the sciatic nerve was transected and repaired, and, in the latter 2 groups, ES was applied after repair. Postoperatively, changes to gene expression from dorsal root ganglia were measured after 24 hours. The number of motoneurons regenerating axons was determined by retrograde labeling at 7 days. Histomorphological analyses of the nerve were performed at 14 days. Function was evaluated serially with use of behavioral tests up to 56 days postoperatively, and relative muscle weight was evaluated., Results: Compared with the no-ES group, both ES groups demonstrated increased regeneration-associated gene expression within dorsal root ganglia. The 10-minute and 60-minute ES groups demonstrated accelerated axon regeneration compared with the no-ES group based on increased numbers of labeled motoneurons regenerating axons (mean difference, 202.0 [95% confidence interval (CI), 17.5 to 386.5] and 219.4 [95% CI, 34.9 to 403.9], respectively) and myelinated axon counts (mean difference, 559.3 [95% CI, 241.1 to 877.5] and 339.4 [95% CI, 21.2 to 657.6], respectively). The 10-minute and 60-minute ES groups had improved behavioral recovery, including on grid-walking analysis, compared with the no-ES group (mean difference, 11.9% [95% CI, 3.8% to 20.0%] and 10.9% [95% CI, 2.9% to 19.0%], respectively). There was no difference between the ES groups in measured outcomes., Conclusions: A 10-minute ES protocol accelerated axon regeneration and facilitated functional recovery., Clinical Relevance: The brief (10-minute) ES protocol provided similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair mice model and merits further studies., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G615)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)
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- 2021
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46. Quantification of Trace-Level Silicon Doping in Al x Ga 1- x N Films Using Wavelength-Dispersive X-Ray Microanalysis.
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Spasevski L, Buse B, Edwards PR, Hunter DA, Enslin J, Foronda HM, Wernicke T, Mehnke F, Parbrook PJ, Kneissl M, and Martin RW
- Abstract
Wavelength-dispersive X-ray (WDX) spectroscopy was used to measure silicon atom concentrations in the range 35-100 ppm [corresponding to (3-9) × 1018 cm-3] in doped AlxGa1-xN films using an electron probe microanalyser also equipped with a cathodoluminescence (CL) spectrometer. Doping with Si is the usual way to produce the n-type conducting layers that are critical in GaN- and AlxGa1-xN-based devices such as LEDs and laser diodes. Previously, we have shown excellent agreement for Mg dopant concentrations in p-GaN measured by WDX with values from the more widely used technique of secondary ion mass spectrometry (SIMS). However, a discrepancy between these methods has been reported when quantifying the n-type dopant, silicon. We identify the cause of discrepancy as inherent sample contamination and propose a way to correct this using a calibration relation. This new approach, using a method combining data derived from SIMS measurements on both GaN and AlxGa1-xN samples, provides the means to measure the Si content in these samples with account taken of variations in the ZAF corrections. This method presents a cost-effective and time-saving way to measure the Si doping and can also benefit from simultaneously measuring other signals, such as CL and electron channeling contrast imaging.
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- 2021
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47. Strigolactones regulate sepal senescence in Arabidopsis.
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Xu X, Jibran R, Wang Y, Dong L, Flokova K, Esfandiari A, McLachlan ARG, Heiser A, Sutherland-Smith AJ, Brummell DA, Bouwmeester HJ, Dijkwel PP, and Hunter DA
- Subjects
- Gene Expression Regulation, Plant, Heterocyclic Compounds, 3-Ring, Lactones, Plant Growth Regulators, Arabidopsis genetics, Arabidopsis metabolism, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism
- Abstract
Flower sepals are critical for flower development and vary greatly in life span depending on their function post-pollination. Very little is known about what controls sepal longevity. Using a sepal senescence mutant screen, we identified two Arabidopsis mutants with delayed senescence directly connecting strigolactones with senescence regulation in a novel floral context that hitherto has not been explored. The mutations were in the strigolactone biosynthetic gene MORE AXILLARY GROWTH1 (MAX1) and in the strigolactone receptor gene DWARF14 (AtD14). The mutation in AtD14 changed the catalytic Ser97 to Phe in the enzyme active site, which is the first mutation of its kind in planta. The lesion in MAX1 was in the haem-iron ligand signature of the cytochrome P450 protein, converting the highly conserved Gly469 to Arg, which was shown in a transient expression assay to substantially inhibit the activity of MAX1. The two mutations highlighted the importance of strigolactone activity for driving to completion senescence initiated both developmentally and in response to carbon-limiting stress, as has been found for the more well-known senescence-associated regulators ethylene and abscisic acid. Analysis of transcript abundance in excised inflorescences during an extended night suggested an intricate relationship among sugar starvation, senescence, and strigolactone biosynthesis and signalling., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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48. Transcriptome Responses of Ripe Cherry Tomato Fruit Exposed to Chilling and Rewarming Identify Reversible and Irreversible Gene Expression Changes.
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Hunter DA, Napier NJ, Erridge ZA, Saei A, Chen RKY, McKenzie MJ, O'Donoghue EM, Hunt M, Favre L, Lill RE, and Brummell DA
- Abstract
Tomato fruit stored below 12°C lose quality and can develop chilling injury upon subsequent transfer to a shelf temperature of 20°C. The more severe symptoms of altered fruit softening, uneven ripening and susceptibility to rots can cause postharvest losses. We compared the effects of exposure to mild (10°C) and severe chilling (4°C) on the fruit quality and transcriptome of 'Angelle', a cherry-type tomato, harvested at the red ripe stage. Storage at 4°C (but not at 10°C) for 27 days plus an additional 6 days at 20°C caused accelerated softening and the development of mealiness, both of which are commonly related to cell wall metabolism. Transcriptome analysis using RNA-Seq identified a range of transcripts encoding enzymes putatively involved in cell wall disassembly whose expression was strongly down-regulated at both 10 and 4°C, suggesting that accelerated softening at 4°C was due to factors unrelated to cell wall disassembly, such as reductions in turgor. In fruit exposed to severe chilling, the reduced transcript abundances of genes related to cell wall modification were predominantly irreversible and only partially restored upon rewarming of the fruit. Within 1 day of exposure to 4°C, large increases occurred in the expression of alternative oxidase, superoxide dismutase and several glutathione S-transferases, enzymes that protect cell contents from oxidative damage. Numerous heat shock proteins and chaperonins also showed large increases in expression, with genes showing peak transcript accumulation after different times of chilling exposure. These changes in transcript abundance were not induced at 10°C, and were reversible upon transfer of the fruit from 4 to 20°C. The data show that genes involved in cell wall modification and cellular protection have differential sensitivity to chilling temperatures, and exhibit different capacities for recovery upon rewarming of the fruit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hunter, Napier, Erridge, Saei, Chen, McKenzie, O’Donoghue, Hunt, Favre, Lill and Brummell.)
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- 2021
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49. Long Acellular Nerve Allografts Cap Transected Nerve to Arrest Axon Regeneration and Alter Upstream Gene Expression in a Rat Neuroma Model.
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Pan D, Bichanich M, Wood IS, Hunter DA, Tintle SM, Davis TA, Wood MD, and Moore AM
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- Allografts transplantation, Animals, Disease Models, Animal, Gene Expression Regulation, Humans, Male, Neuroma genetics, Neuroma pathology, Rats, Sciatic Nerve injuries, Transplantation, Homologous methods, Axons pathology, Nerve Regeneration genetics, Neuroma surgery, Neurosurgical Procedures methods, Sciatic Nerve transplantation
- Abstract
Background: Treatments to manage painful neuroma are needed. An operative strategy that isolates and controls chaotic axonal growth could prevent neuroma. Using long acellular nerve allograft to "cap" damaged nerve could control axonal regeneration and, in turn, regulate upstream gene expression patterns., Methods: Rat sciatic nerve was transected, and the distal nerve end was reversed and ligated to generate a model end-neuroma. Three groups were used to assess their effects immediately following this nerve injury: no treatment (control), traction neurectomy, or 5-cm acellular nerve allograft cap attached to the proximal nerve. Regeneration of axons from the injured nerve was assessed over 5 months and paired with concurrent measurements of gene expression from upstream affected dorsal root ganglia., Results: Both control and traction neurectomy groups demonstrated uncontrolled axon regeneration revealed using Thy1-GFP rat axon imaging and histomorphometric measures of regenerated axons within the most terminal region of regenerated tissue. The acellular nerve allograft group arrested axons within the acellular nerve allograft, where no axons reached the most terminal region even after 5 months. At 5 months, gene expression associated with regeneration and pain sensitization, including Bdnf, cfos, and Gal, was decreased within dorsal root ganglia obtained from the acellular nerve allograft group compared to control or traction neurectomy group dorsal root ganglia., Conclusions: Long acellular nerve allografts to cap a severed nerve arrested axon regeneration within the acellular nerve allograft. This growth arrest corresponded with changes in regenerative and pain-related genes upstream. Acellular nerve allografts may be useful for surgical intervention of neuroma., Competing Interests: Disclosure:Dr. Matthew D. Wood has been the recipient of sponsored research agreements from Checkpoint Surgical, Inc., and has consulted for Foundry Therapeutics, LLC, and The Foundry, LLC. No personal compensation was provided. None of the other authors has any conflicts of interest to disclose., (Copyright © 2021 by the American Society of Plastic Surgeons.)
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- 2021
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50. Neuroma Management: Capping Nerve Injuries With an Acellular Nerve Allograft Can Limit Axon Regeneration.
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Hong T, Wood I, Hunter DA, Yan Y, Mackinnon SE, Wood MD, and Moore AM
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- Allografts, Animals, Nerve Regeneration, Rats, Sciatic Nerve, Axons, Neuroma surgery
- Abstract
Background: Management of painful neuromas continues to challenge clinicians. Controlling axon growth to prevent neuroma has gained considerable traction. A logical extension of this idea is to therefore develop an approach to control and arrest axon growth. Given the limits in axonal regeneration across acellular nerve allografts (ANAs), these constructs could provide a means to reliably terminate axon regeneration from an injured nerve. The purpose of this study was to determine if attaching an ANA to an injured nerve could provide a means to control and limit axon regeneration in a predictable manner. Methods: Twenty (20) adult rats received a sciatic nerve transection, where only the proximal nerve was repaired using an ANA of variable length (0.5, 2.5, and 5.0 cm) or left unrepaired (control). The nerves were harvested 5 weeks post-operatively for gross and histomorphometric analysis. The extent of myelinated axons in regenerated tissue was quantified. Results: At 5 weeks, limited axon regeneration within the ANAs was observed. All lengths of ANAs lead to reduced myelinated axon numbers in the most terminal tissue region compared to untreated injured nerve ( P = .002). Additionally, ANA length 2.5 cm or greater did not contain any axons at the most terminal tissue region. Conclusions: This study demonstrates a proof of concept that ANAs attached to the proximal end of an injured nerve can limit axon growth in a controlled manner. Furthermore, the extent of axon growth from the injured nerve into the ANA is dependent on the ANA length.
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- 2021
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