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Your search keyword '"Mullen, S."' showing total 15 results
Start Over Author "Mullen, S." Publication Type Electronic Resources
15 results on '"Mullen, S."'

1. Experience of the first adult-focussed undiagnosed disease program in Australia (AHA-UDP): solving rare and puzzling genetic disorders is ageless

Author

Wallis, M, Bodek, SD, Munro, J, Rafehi, H, Bennett, MF, Ye, Z, Schneider, A, Gardiner, F, Valente, G, Murdoch, E, Uebergang, E, Hunter, J, Stutterd, C, Huq, A, Salmon, L, Scheffer, I, Eratne, D, Meyn, S, Fong, CY, John, T, Mullen, S, White, SM, Brown, NJ, McGillivray, G, Chen, J, Richmond, C, Hughes, A, Krzesinski, E, Fennell, A, Chambers, B, Santoreneos, R, Le Fevre, A, Hildebrand, MS, Bahlo, M, Christodoulou, J, Delatycki, M, Berkovic, SF, Wallis, M, Bodek, SD, Munro, J, Rafehi, H, Bennett, MF, Ye, Z, Schneider, A, Gardiner, F, Valente, G, Murdoch, E, Uebergang, E, Hunter, J, Stutterd, C, Huq, A, Salmon, L, Scheffer, I, Eratne, D, Meyn, S, Fong, CY, John, T, Mullen, S, White, SM, Brown, NJ, McGillivray, G, Chen, J, Richmond, C, Hughes, A, Krzesinski, E, Fennell, A, Chambers, B, Santoreneos, R, Le Fevre, A, Hildebrand, MS, Bahlo, M, Christodoulou, J, Delatycki, M, and Berkovic, SF

Abstract

BACKGROUND: Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing for children with rare diseases in many centres, but there remains a service gap for adults. The Austin Health Adult Undiagnosed Disease Program (AHA-UDP) was designed to complement existing UDP programs that focus on paediatric rare diseases and address an area of unmet diagnostic need for adults with undiagnosed rare conditions in Victoria, Australia. It was conducted at a large Victorian hospital to demonstrate the benefits of bringing genomic techniques currently used predominantly in a research setting into hospital clinical practice, and identify the benefits of enrolling adults with undiagnosed rare diseases into a UDP program. The main objectives were to identify the causal mutation for a variety of diseases of individuals and families enrolled, and to discover novel disease genes. METHODS: Unsolved patients in whom standard genomic diagnostic techniques such as targeted gene panel, exome-wide next generation sequencing, and/or chromosomal microarray, had already been performed were recruited. Genome sequencing and enhanced genomic analysis from the research setting were applied to aid novel gene discovery. RESULTS: In total, 16/50 (32%) families/cases were solved. One or more candidate variants of uncertain significance were detected in 18/50 (36%) families. No candidate variants were identified in 16/50 (32%) families. Two novel disease genes (TOP3B, PRKACB) and two novel genotype-phenotype correlations (NARS, and KMT2C genes) were identified. Three out of eight patients with suspected mosaic tuberous sclerosis complex had their diagnosis confirmed which provided reproductive options for two patients. The utility of confirming diagnoses for patients with mosaic conditions (using high read depth sequencing and ddPCR) was not specifically envisaged at the onset of the project, but the flexibility to offer recruitment and analyses on

Published
2024

2. An iPSC line (FINi003-A) from a male with late-onset developmental and epileptic encephalopathy caused by a heterozygous p.E1211K variant in the SCN2A gene encoding the voltage-gated sodium channel Nav1.2

Author

Ovchinnikov, DA, Jong, S, Cuddy, C, Dalby, K, Devinsky, O, Mullen, S, Maljevic, S, Petrou, S, Ovchinnikov, DA, Jong, S, Cuddy, C, Dalby, K, Devinsky, O, Mullen, S, Maljevic, S, and Petrou, S

Abstract

Many developmental and epileptic encephalopathies (DEEs) result from variants in cation channel genes. Using mRNA transfection, we generated and characterised an induced pluripotent stem cell (iPSC) line from the fibroblasts of a male late-onset DEE patient carrying a heterozygous missense variant (E1211K) in Nav1.2(SCN2A) protein. The iPSC line displays features characteristic of the human iPSCs, colony morphology and expression of pluripotency-associated marker genes, ability to produce derivatives of all three embryonic germ layers, and normal karyotype without SNP array-detectable abnormalities. We anticipate that this iPSC line will aid in the modelling and development of precision therapies for this debilitating condition.

Published
2024

3. Changing the culture: a qualitative study exploring research capacity in local government

Author

Homer, C, Woodall, J, Freeman, C, South, J, Cooke, J, Holliday, J, Hartley, A, Mullen, S, Homer, C, Woodall, J, Freeman, C, South, J, Cooke, J, Holliday, J, Hartley, A, and Mullen, S

Abstract

Background Local government has become a key constituent for addressing health inequalities and influencing the health of individuals and communities in England. Lauded as an effective approach to tackle the multiple determinants of health, there are concerns that generating and utilising research evidence to inform decision-making and action is a challenge. This research was conducted in a local authority situated in the north of England and addressed the research question – ‘What is the capacity to collaborate and deliver research?’. The study explored the assets that exist to foster a stronger research culture, identified barriers and opportunities for developing research capacity, and how a sustainable research system could be developed to impact on local residents’ health and reduce health inequalities. Methods This was a qualitative study utilising semi-structured interviews and focus groups. The study used an embedded researcher (ER) who was digitally embedded within the local authority for four months to conduct the data collection. Senior Managers were purposively sampled from across the local authority to take part in interviews. Three focus groups included representation from across the local authority. Framework analysis was conducted to develop the themes which were informed by the Research Capacity Development framework. Results Tensions between research led decision making and the political and cultural context of local government were identified as a barrier to developing research which addressed health inequalities. Research was not prioritised through an organisational strategy and was led sporadically by research active employees. A recognition across leaders that a culture shift to an organisation which used research evidence to develop policy and commission services was needed. Building relationships and infrastructure across local government, place-based collaborators and academic institutions was required. The embedded researcher approach is o

Published
2022

4. Somatic IDH1 variant ( p.R132C) in an adult male with Maffucci syndrome

Author

Brown, NJ, Ye, Z, Stutterd, C, Jayasinghe, SI, Schneider, A, Mullen, S, Mandelstam, SA, Hildebrand, MS, Brown, NJ, Ye, Z, Stutterd, C, Jayasinghe, SI, Schneider, A, Mullen, S, Mandelstam, SA, and Hildebrand, MS

Abstract

Maffucci syndrome is a rare, highly variable somatic mosaic condition, and well-known cancer-related gain-of-function variants in either the IDH1 or IDH2 genes have been found in the affected tissues of most reported individuals. Features include benign enchondroma and spindle-cell hemangioma, with a recognized increased risk of various malignancies. Fewer than 200 affected individuals have been reported; therefore, accurate estimates of malignancy risk are difficult to quantify and recommended surveillance guidelines are not available. The same gain-of-function IDH1 and IDH2 variants are also implicated in a variety of other benign and malignant tumors. An adult male presented with several soft palpable lesions on the right upper limb. Imaging and histopathology raised the possibility of Maffucci syndrome. DNA was extracted from peripheral blood lymphocytes and tissue surgically resected from a spindle-cell hemangioma. Sanger sequencing and droplet digital polymerase chain reaction (PCR) analysis of the IDH1 gene were performed. We identified a somatic mosaic c.394C > T (p.R132C) variant in exon 5 of IDH1, in DNA derived from hemangioma tissue at ∼17% variant allele fraction. This variant was absent in DNA derived from blood. This variant has been identified in the affected tissue of most reported individuals with Maffucci syndrome. Although this individual has a potentially targetable variant, and there is a recognized risk of malignant transformation in this condition, a decision was made not to intervene with an IDH1 inhibitor. The reasons and prospects for therapy in this condition are discussed.

Published
2021

5. Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Author

Sadleir, LG, de Valles-Ibanez, G, King, C, Coleman, M, Mossman, S, Paterson, S, Nguyen, J, Berkovic, SF, Mullen, S, Bahlo, M, Hildebrand, MS, Mefford, HC, Scheffer, IE, Sadleir, LG, de Valles-Ibanez, G, King, C, Coleman, M, Mossman, S, Paterson, S, Nguyen, J, Berkovic, SF, Mullen, S, Bahlo, M, Hildebrand, MS, Mefford, HC, and Scheffer, IE

Abstract

Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.

Published
2020

6. The operational environment and rotational acceleration of asteroid (101955) Bennu from OSIRIS-REx observations

Author

Hergenrother, CW, Maleszewski, CK, Nolan, MC, Li, J-Y, d'Aubigny, CYD, Shelly, FC, Howell, ES, Kareta, TR, Izawa, MRM, Barucci, MA, Bierhaus, EB, Campins, H, Chesley, SR, Clark, BE, Christensen, EJ, DellaGiustina, DN, Fornasier, S, Golish, DR, Hartzell, CM, Rizk, B, Scheeres, DJ, Smith, PH, Zou, X-D, Lauretta, DS, Highsmith, DE, Small, J, Vokrouhlicky, D, Bowles, NE, Brown, E, Hanna, KLD, Warren, T, Brunet, C, Chicoine, RA, Desjardins, S, Gaudreau, D, Haltigin, T, Millington-Veloza, S, Rubi, A, Aponte, J, Gorius, N, Lunsford, A, Allen, B, Grindlay, J, Guevel, D, Hoak, D, Hong, J, Schrader, DL, Bayron, J, Golubov, O, Sanchez, P, Stromberg, J, Hirabayashi, M, Oliver, S, Rascon, M, Harch, A, Joseph, J, Squyres, S, Richardson, D, Emery, JP, McGraw, L, Ghent, R, Binzel, RP, Al Asad, MM, Johnson, CL, Philpott, L, Susorney, HCM, Cloutis, EA, Hanna, RD, Connolly, HC, Ciceri, F, Hildebrand, AR, Ibrahim, E-M, Breitenfeld, L, Glotch, T, Rogers, AD, Ferrone, S, Thomas, CA, Fernandez, Y, Chang, W, Cheuvront, A, Trang, D, Tachibana, S, Yurimoto, H, Brucato, JR, Poggiali, G, Pajola, M, Dotto, E, Epifani, EM, Crombie, MK, Lantz, C, de Leon, J, Licandro, J, Rizos Garcia, JL, Clemett, S, Thomas-Keprta, K, Van Wal, S, Yoshikawa, M, Bellerose, J, Bhaskaran, S, Boyles, C, Elder, CM, Farnocchia, D, Harbison, A, Kennedy, B, Knight, A, Martinez-Vlasoff, N, Mastrodemos, N, McElrath, T, Owen, W, Park, R, Rush, B, Swanson, L, Takahashi, Y, Velez, D, Yetter, K, Thayer, C, Adam, C, Antreasian, P, Bauman, J, Bryan, C, Carcich, B, Corvin, M, Geeraert, J, Hoffman, J, Leonard, JM, Lessac-Chenen, E, Levine, A, McAdams, J, McCarthy, L, Nelson, D, Page, B, Pelgrift, J, Sahr, E, Stakkestad, K, Stanbridge, D, Wibben, D, Williams, B, Williams, K, Wolff, P, Hayne, P, Kubitschek, D, Deshapriya, JDP, Fulchignoni, M, Hasselmann, P, Merlin, F, Praet, A, Billett, O, Boggs, A, Buck, B, Carlson-Kelly, S, Cerna, J, Chaffin, K, Church, E, Coltrin, M, Daly, J, Deguzman, A, Dubisher, R, Eckart, D, Ellis, D, Falkenstern, P, Fisher, A, Fisher, ME, Fleming, P, Fortney, K, Francis, S, Freund, S, Gonzales, S, Haas, P, Hasten, A, Hauf, D, Hilbert, A, Howell, D, Jaen, F, Jayakody, N, Jenkins, M, Johnson, K, Lefevre, M, Ma, H, Mario, C, Martin, K, May, C, McGee, M, Miller, B, Miller, C, Miller, G, Mirfakhrai, A, Muhle, E, Norman, C, Olds, R, Parish, C, Ryle, M, Schmitzer, M, Sherman, P, Skeen, M, Susak, M, Sutter, B, Tran, Q, Welch, C, Witherspoon, R, Wood, J, Zareski, J, Arvizu-Jakubicki, M, Asphaug, E, Audi, E, Ballouz, R-L, Bandrowski, R, Becker, KJ, Becker, TL, Bendall, S, Bennett, CA, Bloomenthal, H, Blum, D, Boynton, W, Brodbeck, J, Burke, KN, Chojnacki, M, Colpo, A, Contreras, J, Cutts, J, Dean, D, Diallo, B, Drinnon, D, Drozd, K, Enos, HL, Enos, R, Fellows, C, Ferro, T, Fisher, MR, Fitzgibbon, G, Fitzgibbon, M, Forelli, J, Forrester, T, Galinsky, I, Garcia, R, Gardner, A, Habib, N, Hamara, D, Hammond, D, Hanley, K, Harshman, K, Herzog, K, Hill, D, Hoekenga, C, Hooven, S, Huettner, E, Janakus, A, Jones, J, Kidd, J, Kingsbury, K, Balram-Knutson, SS, Koelbel, L, Kreiner, J, Lambert, D, Lewin, C, Lovelace, B, Loveridge, M, Lujan, M, Malhotra, R, Marchese, K, McDonough, E, Mogk, N, Morrison, V, Morton, E, Munoz, R, Nelson, J, Padilla, J, Pennington, R, Polit, A, Ramos, N, Reddy, V, Riehl, M, Roper, HL, Salazar, S, Schwartz, SR, Selznick, S, Shultz, N, Stewart, S, Sutton, S, Swindle, T, Tang, YH, Westermann, M, Wolner, CW, Worden, D, Zega, T, Zeszut, Z, Bjurstrom, A, Bloomquist, L, Dickinson, C, Keates, E, Liang, J, Nifo, V, Taylor, A, Teti, F, Caplinger, M, Bowles, H, Carter, S, Dickenshied, S, Doerres, D, Fisher, T, Hagee, W, Hill, J, Miner, M, Noss, D, Piacentine, N, Smith, M, Toland, A, Wren, P, Bernacki, M, Munoz, DP, Watanabe, S, Sandford, SA, Aqueche, A, Ashman, B, Barker, M, Bartels, A, Berry, K, Bos, B, Burns, R, Calloway, A, Carpenter, R, Castro, N, Cosentino, R, Donaldson, J, Dworkin, JP, Cook, JE, Emr, C, Everett, D, Fennell, D, Fleshman, K, Folta, D, Gallagher, D, Garvin, J, Getzandanner, K, Glavin, D, Hull, S, Hyde, K, Ido, H, Ingegneri, A, Jones, N, Kaotira, P, Lim, LF, Liounis, A, Lorentson, C, Lorenz, D, Lyzhoft, J, Mazarico, EM, Mink, R, Moore, W, Moreau, M, Mullen, S, Nagy, J, Neumann, G, Nuth, J, Poland, D, Reuter, DC, Rhoads, L, Rieger, S, Rowlands, D, Sallitt, D, Scroggins, A, Shaw, G, Simon, AA, Swenson, J, Vasudeva, P, Wasser, M, Zellar, R, Grossman, J, Johnston, G, Morris, M, Wendel, J, Burton, A, Keller, LP, McNamara, L, Messenger, S, Nakamura-Messenger, K, Nguyen, A, Righter, K, Queen, E, Bellamy, K, Dill, K, Gardner, S, Giuntini, M, Key, B, Kissell, J, Patterson, D, Vaughan, D, Wright, B, Gaskell, RW, Le Corre, L, Molaro, JL, Palmer, EE, Siegler, MA, Tricarico, P, Weirich, JR, Ireland, T, Tait, K, Bland, P, Anwar, S, Bojorquez-Murphy, N, Christensen, PR, Haberle, CW, Mehall, G, Rios, K, Franchi, I, Rozitis, B, Beddingfield, CB, Marshall, J, Brack, DN, French, AS, McMahon, JW, Jawin, ER, McCoy, TJ, Russell, S, Killgore, M, Bottke, WF, Hamilton, VE, Kaplan, HH, Walsh, KJ, Bandfield, JL, Clark, BC, Chodas, M, Lambert, M, Masterson, RA, Daly, MG, Freemantle, J, Seabrook, JA, Barnouin, OS, Craft, K, Daly, RT, Ernst, C, Espiritu, RC, Holdridge, M, Jones, M, Nair, AH, Nguyen, L, Peachey, J, Perry, ME, Plescia, J, Roberts, JH, Steele, R, Turner, R, Backer, J, Edmundson, K, Mapel, J, Milazzo, M, Sides, S, Manzoni, C, May, B, Delbo, M, Libourel, G, Michel, P, Ryan, A, Thuillet, F, Marty, B, Hergenrother, CW, Maleszewski, CK, Nolan, MC, Li, J-Y, d'Aubigny, CYD, Shelly, FC, Howell, ES, Kareta, TR, Izawa, MRM, Barucci, MA, Bierhaus, EB, Campins, H, Chesley, SR, Clark, BE, Christensen, EJ, DellaGiustina, DN, Fornasier, S, Golish, DR, Hartzell, CM, Rizk, B, Scheeres, DJ, Smith, PH, Zou, X-D, Lauretta, DS, Highsmith, DE, Small, J, Vokrouhlicky, D, Bowles, NE, Brown, E, Hanna, KLD, Warren, T, Brunet, C, Chicoine, RA, Desjardins, S, Gaudreau, D, Haltigin, T, Millington-Veloza, S, Rubi, A, Aponte, J, Gorius, N, Lunsford, A, Allen, B, Grindlay, J, Guevel, D, Hoak, D, Hong, J, Schrader, DL, Bayron, J, Golubov, O, Sanchez, P, Stromberg, J, Hirabayashi, M, Oliver, S, Rascon, M, Harch, A, Joseph, J, Squyres, S, Richardson, D, Emery, JP, McGraw, L, Ghent, R, Binzel, RP, Al Asad, MM, Johnson, CL, Philpott, L, Susorney, HCM, Cloutis, EA, Hanna, RD, Connolly, HC, Ciceri, F, Hildebrand, AR, Ibrahim, E-M, Breitenfeld, L, Glotch, T, Rogers, AD, Ferrone, S, Thomas, CA, Fernandez, Y, Chang, W, Cheuvront, A, Trang, D, Tachibana, S, Yurimoto, H, Brucato, JR, Poggiali, G, Pajola, M, Dotto, E, Epifani, EM, Crombie, MK, Lantz, C, de Leon, J, Licandro, J, Rizos Garcia, JL, Clemett, S, Thomas-Keprta, K, Van Wal, S, Yoshikawa, M, Bellerose, J, Bhaskaran, S, Boyles, C, Elder, CM, Farnocchia, D, Harbison, A, Kennedy, B, Knight, A, Martinez-Vlasoff, N, Mastrodemos, N, McElrath, T, Owen, W, Park, R, Rush, B, Swanson, L, Takahashi, Y, Velez, D, Yetter, K, Thayer, C, Adam, C, Antreasian, P, Bauman, J, Bryan, C, Carcich, B, Corvin, M, Geeraert, J, Hoffman, J, Leonard, JM, Lessac-Chenen, E, Levine, A, McAdams, J, McCarthy, L, Nelson, D, Page, B, Pelgrift, J, Sahr, E, Stakkestad, K, Stanbridge, D, Wibben, D, Williams, B, Williams, K, Wolff, P, Hayne, P, Kubitschek, D, Deshapriya, JDP, Fulchignoni, M, Hasselmann, P, Merlin, F, Praet, A, Billett, O, Boggs, A, Buck, B, Carlson-Kelly, S, Cerna, J, Chaffin, K, Church, E, Coltrin, M, Daly, J, Deguzman, A, Dubisher, R, Eckart, D, Ellis, D, Falkenstern, P, Fisher, A, Fisher, ME, Fleming, P, Fortney, K, Francis, S, Freund, S, Gonzales, S, Haas, P, Hasten, A, Hauf, D, Hilbert, A, Howell, D, Jaen, F, Jayakody, N, Jenkins, M, Johnson, K, Lefevre, M, Ma, H, Mario, C, Martin, K, May, C, McGee, M, Miller, B, Miller, C, Miller, G, Mirfakhrai, A, Muhle, E, Norman, C, Olds, R, Parish, C, Ryle, M, Schmitzer, M, Sherman, P, Skeen, M, Susak, M, Sutter, B, Tran, Q, Welch, C, Witherspoon, R, Wood, J, Zareski, J, Arvizu-Jakubicki, M, Asphaug, E, Audi, E, Ballouz, R-L, Bandrowski, R, Becker, KJ, Becker, TL, Bendall, S, Bennett, CA, Bloomenthal, H, Blum, D, Boynton, W, Brodbeck, J, Burke, KN, Chojnacki, M, Colpo, A, Contreras, J, Cutts, J, Dean, D, Diallo, B, Drinnon, D, Drozd, K, Enos, HL, Enos, R, Fellows, C, Ferro, T, Fisher, MR, Fitzgibbon, G, Fitzgibbon, M, Forelli, J, Forrester, T, Galinsky, I, Garcia, R, Gardner, A, Habib, N, Hamara, D, Hammond, D, Hanley, K, Harshman, K, Herzog, K, Hill, D, Hoekenga, C, Hooven, S, Huettner, E, Janakus, A, Jones, J, Kidd, J, Kingsbury, K, Balram-Knutson, SS, Koelbel, L, Kreiner, J, Lambert, D, Lewin, C, Lovelace, B, Loveridge, M, Lujan, M, Malhotra, R, Marchese, K, McDonough, E, Mogk, N, Morrison, V, Morton, E, Munoz, R, Nelson, J, Padilla, J, Pennington, R, Polit, A, Ramos, N, Reddy, V, Riehl, M, Roper, HL, Salazar, S, Schwartz, SR, Selznick, S, Shultz, N, Stewart, S, Sutton, S, Swindle, T, Tang, YH, Westermann, M, Wolner, CW, Worden, D, Zega, T, Zeszut, Z, Bjurstrom, A, Bloomquist, L, Dickinson, C, Keates, E, Liang, J, Nifo, V, Taylor, A, Teti, F, Caplinger, M, Bowles, H, Carter, S, Dickenshied, S, Doerres, D, Fisher, T, Hagee, W, Hill, J, Miner, M, Noss, D, Piacentine, N, Smith, M, Toland, A, Wren, P, Bernacki, M, Munoz, DP, Watanabe, S, Sandford, SA, Aqueche, A, Ashman, B, Barker, M, Bartels, A, Berry, K, Bos, B, Burns, R, Calloway, A, Carpenter, R, Castro, N, Cosentino, R, Donaldson, J, Dworkin, JP, Cook, JE, Emr, C, Everett, D, Fennell, D, Fleshman, K, Folta, D, Gallagher, D, Garvin, J, Getzandanner, K, Glavin, D, Hull, S, Hyde, K, Ido, H, Ingegneri, A, Jones, N, Kaotira, P, Lim, LF, Liounis, A, Lorentson, C, Lorenz, D, Lyzhoft, J, Mazarico, EM, Mink, R, Moore, W, Moreau, M, Mullen, S, Nagy, J, Neumann, G, Nuth, J, Poland, D, Reuter, DC, Rhoads, L, Rieger, S, Rowlands, D, Sallitt, D, Scroggins, A, Shaw, G, Simon, AA, Swenson, J, Vasudeva, P, Wasser, M, Zellar, R, Grossman, J, Johnston, G, Morris, M, Wendel, J, Burton, A, Keller, LP, McNamara, L, Messenger, S, Nakamura-Messenger, K, Nguyen, A, Righter, K, Queen, E, Bellamy, K, Dill, K, Gardner, S, Giuntini, M, Key, B, Kissell, J, Patterson, D, Vaughan, D, Wright, B, Gaskell, RW, Le Corre, L, Molaro, JL, Palmer, EE, Siegler, MA, Tricarico, P, Weirich, JR, Ireland, T, Tait, K, Bland, P, Anwar, S, Bojorquez-Murphy, N, Christensen, PR, Haberle, CW, Mehall, G, Rios, K, Franchi, I, Rozitis, B, Beddingfield, CB, Marshall, J, Brack, DN, French, AS, McMahon, JW, Jawin, ER, McCoy, TJ, Russell, S, Killgore, M, Bottke, WF, Hamilton, VE, Kaplan, HH, Walsh, KJ, Bandfield, JL, Clark, BC, Chodas, M, Lambert, M, Masterson, RA, Daly, MG, Freemantle, J, Seabrook, JA, Barnouin, OS, Craft, K, Daly, RT, Ernst, C, Espiritu, RC, Holdridge, M, Jones, M, Nair, AH, Nguyen, L, Peachey, J, Perry, ME, Plescia, J, Roberts, JH, Steele, R, Turner, R, Backer, J, Edmundson, K, Mapel, J, Milazzo, M, Sides, S, Manzoni, C, May, B, Delbo, M, Libourel, G, Michel, P, Ryan, A, Thuillet, F, and Marty, B

Abstract

During its approach to asteroid (101955) Bennu, NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft surveyed Bennu's immediate environment, photometric properties, and rotation state. Discovery of a dusty environment, a natural satellite, or unexpected asteroid characteristics would have had consequences for the mission's safety and observation strategy. Here we show that spacecraft observations during this period were highly sensitive to satellites (sub-meter scale) but reveal none, although later navigational images indicate that further investigation is needed. We constrain average dust production in September 2018 from Bennu's surface to an upper limit of 150 g s-1 averaged over 34 min. Bennu's disk-integrated photometric phase function validates measurements from the pre-encounter astronomical campaign. We demonstrate that Bennu's rotation rate is accelerating continuously at 3.63 ± 0.52 × 10-6 degrees day-2, likely due to the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect, with evolutionary implications.

Published
2019

7. Real-world clinical utility and impact on clinical decision-making of coronary computed tomography angiography-derived fractional flow reserve: lessons from the ADVANCE Registry

Author

Fairbairn, T.A. (Timothy A.), Nieman, K. (Koen), Akasaka, T. (Takashi), Nørgaard, B. (Bjarne), Berman, D.S. (Daniel), Raff, G.L. (Gilbert), Hurwitz-Koweek, L.M. (Lynne M.), Pontone, G. (Gianluca), Kawasaki, T. (Tomohiro), Sand, N.P. (Niels Peter), Jensen, J.M. (Jesper M.), Amano, T. (Tetsuya), Poon, M. (Michael), Altern Ovrehus, K. (Kristian), Sonck, J. (Jeroen), Rabbat, M. (Mark), Mullen, S. (Sarah), Bruyne, B. (Bernard) de, Rogers, C. (Campbell), Matsuo, H. (Hitoshi), Bax, J.J. (Jeroen), Leipsic, J. (Jonathon), Patel, M.R. (Manesh R.), Fairbairn, T.A. (Timothy A.), Nieman, K. (Koen), Akasaka, T. (Takashi), Nørgaard, B. (Bjarne), Berman, D.S. (Daniel), Raff, G.L. (Gilbert), Hurwitz-Koweek, L.M. (Lynne M.), Pontone, G. (Gianluca), Kawasaki, T. (Tomohiro), Sand, N.P. (Niels Peter), Jensen, J.M. (Jesper M.), Amano, T. (Tetsuya), Poon, M. (Michael), Altern Ovrehus, K. (Kristian), Sonck, J. (Jeroen), Rabbat, M. (Mark), Mullen, S. (Sarah), Bruyne, B. (Bernard) de, Rogers, C. (Campbell), Matsuo, H. (Hitoshi), Bax, J.J. (Jeroen), Leipsic, J. (Jonathon), and Patel, M.R. (Manesh R.)

Abstract

Methods and results: A total of 5083 patients with symptoms concerning for coronary artery disease (CAD) and atherosclerosis on CCTA were enrolled at 38 international sites from 15 July 2015 to 20 October 2017. Demographics, symptom status, CCTA and FFRCT findings, treatment plans, and 90 days outcomes were recorded. The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management plans occurred in 66.9% [confidence interval (CI): 64.8-67.6] of patients. Non-obstructive coronary disease was significantly lower in ICA patients with FFRCT ≤0.80 (14.4%) compared to patients with FFRCT >0.80 (43.8%, odds ratio 0.19, CI: 0.15-0.25, P < 0.001). In total, 72.3% of subjects undergoing ICA with FFRCT ≤0.80 were revascularized. No death/myocardial infarction (MI) occurred within 90 days in patients with FFRCT >0.80 (n = 1529), whereas 19 (0.6%) MACE [hazard ratio (HR) 19.75, CI: 1.19-326, P = 0.0008] and 14 (0.3%) death/MI (HR 14.68, CI 0.88-246, P = 0.039) occurred in subjects with an FFRCT ≤0.80.Conclusions: In a large international multicentre population, FFRCT modified treatment recommendation in two-thirds of subjects as compared to CCTA alone, was associated with less negative ICA, predicted revascularization, and identified subjects at low risk of adverse events through 90 days.Aims: Non-invasive assessment of stable chest pain patients is a critical determinant of resource utilization and clinical outcomes. Increasingly coronary computed tomography angiography (CCTA) with selective CCTA-derived fractional flow reserve (FFRCT) is being used. The ADVANCE Registry, is a large prospective examination of using a CCTA and FFRCT diagnostic pathway in real-world settings, with the aim of determining the impact of this pathway on decision-making, downstream invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular events (MACE).

Published
2018
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8. Real-world clinical utility and impact on clinical decision-making of coronary computed tomography angiography-derived fractional flow reserve: lessons from the ADVANCE Registry

Author

Fairbairn, TA, Nieman, Koen, Akasaka, T, Norgaard, BL, Berman, DS, Raff, G, Hurwitz-Koweek, LM, Pontone, G, Kawasaki, T, Sand, NP, Jensen, JM, Amano, T, Poon, M, Ovrehus, K, Sonck, J, Rabbat, M, Mullen, S, de Bruyne, B, Rogers, C, Matsuo, H, Bax, JJ, Leipsic, J, Patel, MR, Fairbairn, TA, Nieman, Koen, Akasaka, T, Norgaard, BL, Berman, DS, Raff, G, Hurwitz-Koweek, LM, Pontone, G, Kawasaki, T, Sand, NP, Jensen, JM, Amano, T, Poon, M, Ovrehus, K, Sonck, J, Rabbat, M, Mullen, S, de Bruyne, B, Rogers, C, Matsuo, H, Bax, JJ, Leipsic, J, and Patel, MR

Published
2018

9. Hybridization and speciation

Author

Abbott, R., Albach, D., Ansell, S., Arntzen, J. W., Baird, S. J. E., Bierne, N., Boughman, J., Brelsford, A., Buerkle, C. A., Buggs, R., Butlin, R. K., Dieckmann, U., Eroukhmanoff, F., Grill, A., Cahan, S. H., Hermansen, J. S., Hewitt, G., Hudson, A. G., Jiggins, C., Jones, J., Keller, B., Marczewski, T., Mallet, J., Martinez-Rodriguez, P., Möst, M., Mullen, S., Nichols, R., Nolte, A. W., Parisod, C., Pfennig, K., Rice, A. M., Ritchie, M. G., Seifert, B., Smadja, C. M., Stelkens, R., Szymura, J. M., Väinölä, R., Wolf, Jochen B. W., Zinner, D., Abbott, R., Albach, D., Ansell, S., Arntzen, J. W., Baird, S. J. E., Bierne, N., Boughman, J., Brelsford, A., Buerkle, C. A., Buggs, R., Butlin, R. K., Dieckmann, U., Eroukhmanoff, F., Grill, A., Cahan, S. H., Hermansen, J. S., Hewitt, G., Hudson, A. G., Jiggins, C., Jones, J., Keller, B., Marczewski, T., Mallet, J., Martinez-Rodriguez, P., Möst, M., Mullen, S., Nichols, R., Nolte, A. W., Parisod, C., Pfennig, K., Rice, A. M., Ritchie, M. G., Seifert, B., Smadja, C. M., Stelkens, R., Szymura, J. M., Väinölä, R., Wolf, Jochen B. W., and Zinner, D.

Abstract

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.

Published
2013
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10. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Author

Steffens, M, Leu, C, Ruppert, A-K, Zara, F, Striano, P, Robbiano, A, Capovilla, G, Tinuper, P, Gambardella, A, Bianchi, A, La Neve, A, Crichiutti, G, de Kovel, CGF, Trenite, DK-N, de Haan, G-J, Lindhout, D, Gaus, V, Schmitz, B, Janz, D, Weber, YG, Becker, F, Lerche, H, Steinhoff, BJ, Kleefuss-Lie, AA, Kunz, WS, Surges, R, Elger, CE, Muhle, H, von Spiczak, S, Ostertag, P, Helbig, I, Stephani, U, Moller, RS, Hjalgrim, H, Dibbens, LM, Bellows, S, Oliver, K, Mullen, S, Scheffer, IE, Berkovic, SF, Everett, KV, Gardiner, MR, Marini, C, Guerrini, R, Lehesjoki, A-E, Siren, A, Guipponi, M, Malafosse, A, Thomas, P, Nabbout, R, Baulac, S, Leguern, E, Guerrero, R, Serratosa, JM, Reif, PS, Rosenow, F, Moerzinger, M, Feucht, M, Zimprich, F, Kapser, C, Schankin, CJ, Suls, A, Smets, K, De Jonghe, P, Jordanova, A, Caglayan, H, Yapici, Z, Yalcin, DA, Baykan, B, Bebek, N, Ozbek, U, Gieger, C, Wichmann, H-E, Balschun, T, Ellinghaus, D, Franke, A, Meesters, C, Becker, T, Wienker, TF, Hempelmann, A, Schulz, H, Rueschendorf, F, Leber, M, Pauck, SM, Trucks, H, Toliat, MR, Nuernberg, P, Avanzini, G, Koeleman, BPC, Sander, T, Steffens, M, Leu, C, Ruppert, A-K, Zara, F, Striano, P, Robbiano, A, Capovilla, G, Tinuper, P, Gambardella, A, Bianchi, A, La Neve, A, Crichiutti, G, de Kovel, CGF, Trenite, DK-N, de Haan, G-J, Lindhout, D, Gaus, V, Schmitz, B, Janz, D, Weber, YG, Becker, F, Lerche, H, Steinhoff, BJ, Kleefuss-Lie, AA, Kunz, WS, Surges, R, Elger, CE, Muhle, H, von Spiczak, S, Ostertag, P, Helbig, I, Stephani, U, Moller, RS, Hjalgrim, H, Dibbens, LM, Bellows, S, Oliver, K, Mullen, S, Scheffer, IE, Berkovic, SF, Everett, KV, Gardiner, MR, Marini, C, Guerrini, R, Lehesjoki, A-E, Siren, A, Guipponi, M, Malafosse, A, Thomas, P, Nabbout, R, Baulac, S, Leguern, E, Guerrero, R, Serratosa, JM, Reif, PS, Rosenow, F, Moerzinger, M, Feucht, M, Zimprich, F, Kapser, C, Schankin, CJ, Suls, A, Smets, K, De Jonghe, P, Jordanova, A, Caglayan, H, Yapici, Z, Yalcin, DA, Baykan, B, Bebek, N, Ozbek, U, Gieger, C, Wichmann, H-E, Balschun, T, Ellinghaus, D, Franke, A, Meesters, C, Becker, T, Wienker, TF, Hempelmann, A, Schulz, H, Rueschendorf, F, Leber, M, Pauck, SM, Trucks, H, Toliat, MR, Nuernberg, P, Avanzini, G, Koeleman, BPC, and Sander, T

Abstract

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.

Published
2012

11. Generic Adversary Characteristics and the Potential Threat to Licensed Nuclear Activities from Insiders

Author

NUCLEAR REGULATORY COMMISSION WASHINGTON DC, Mullen, S., NUCLEAR REGULATORY COMMISSION WASHINGTON DC, and Mullen, S.

Abstract

NRC has been charged by Congress with the responsibility for provision and maintenance of safeguards against theft and sabotage of licensed nuclear materials and facilities. In the discharge of this mandate, the Commission directed the Division of Safeguards to undertake two studies: one aimed at a systematic determination of the characteristics of potential adversaries to nuclear programs and the second aimed at a more detailed examination of the potential insider adversary. The first study, entitled Generic Adversary Characteristics (GAC), was intended as an initial NRC effort at threat definition. It entails an analysis characteristics associated with subnational conventional crimes and terrorist actions that could be analogous to potential nuclear events. The Insider Study addresses the two types of insider crime that are the primary concern of nuclear safeguards--theft and sabotage-- and focuses on the insider adversary, one whose authorized access to a facility or activity may be exploited by him or others in the commission of a crime. The three objectives of the study are shown here. Data used in fulfilling these objectives were derived primarily from case histories of insider crime, but also from expert opinion and from non-NRC studies., This article is from 'Proceedings of the Symposium on the Role of Behavioral Science on Physical Security (6th Annual), Held at Springfield, Virginia, 3-4 June l981', AD-A141 426, p99-109.

Published
1981

12. Reliability of Nondestructive Inspection (NDI) of Aircraft Engine Components.

Author

MARTIN MARIETTA AEROSPACE DENVER CO, Rummel,W. D., Mullen,S. J., Christner,B. K., Ross,F. B., Muthart,R. E., MARTIN MARIETTA AEROSPACE DENVER CO, Rummel,W. D., Mullen,S. J., Christner,B. K., Ross,F. B., and Muthart,R. E.

Abstract

During Phase III, on-site NDI assessments were conducted at the San Antonio Air Logistics Center at Kelly AFB, and at Oklahoma City Air Logistics Center at Tinker AFB. Assessments were performed by subjecting the representative test gas turbine engine components and specimens to production NDI procedures that are routinely applied to engine components and documenting the response/detection of each flaw in the test component. Assessments were performed and documented by methods that would support a statistically significant data sample size and would enable assessment of characteristic parameters of each NDI procedure. During Phase IV, the data were analyzed and combined to establish the baseline capabilities and reliability of NDI procedures as they were applied in production. During performance of the Phase III task, penetrant material and penetrant processing variables were identified and an off-line assessment was initiated to characterize inspection materials and processing parameters and interactions of the various parameters as a function of NDI capability. Prototype laboratory instrumentation was designed, built and utilized to process samples of penetrant processing materials that were taken at the time of assessment of each penetrant procedure. The results of the off-line processing were correlated to the probability of detection (POD) analyses and were integrated into the overall conclusions and recommendations.

Published
1984

13. Effects of Propranolol on Time of Useful Function (TUF) in Rats

Author

FEDERAL AVIATION ADMINISTRATION WASHINGTON D C OFFICE OF AVIATION MEDICINE, Higgins,E A, McKenzie,J M, Funkhouser,G E, Mullen,S R, FEDERAL AVIATION ADMINISTRATION WASHINGTON D C OFFICE OF AVIATION MEDICINE, Higgins,E A, McKenzie,J M, Funkhouser,G E, and Mullen,S R

Abstract

To assess the effects of propranolol on tolerance to rapid decompression, a series of experiments was conducted measuring time of useful function (TUF) in rats exposed to a rapid decompression profile in an altitude chamber. In other experiments TUF was measured for rats exposed to an oxygen/nitrogen gas mixture which produced a hypoxic condition equivalent to that in the decompression experiments. The findings were: (1) Rats become less tolerant to hypoxia of an onset rate comparable to that of rapid decompression when given propranolol, and this intolerance is further exacerbated by an increase in physical exertion. (2) Younger animals are more susceptible to this type of hypoxia, but propranolol has no greater effect on hypoxia tolerance in younger animals. (3) None of the reduced tolerance can be attributed to a shift in the oxyhemoglobin dissociation curve. In rats the curve is shifted slightly to the left, whereas in man there is a reported shift to the right. Because propranolol impairs tolerance to hypoxia in experimental animals, it is important to assess its effects on human tolerance. (Author)

Published
1979

15. Effects of lithium carbonate on performance and biomedical functions.

Author

United States. Office of Aviation Medicine, Higgins, E., Chiles, W., McKenzie, J., Davis, A., Funkhouser, G., Jennings, A., Mullen, S., Fowler, P., Civil Aeromedical Institute, United States. Office of Aviation Medicine, Higgins, E., Chiles, W., McKenzie, J., Davis, A., Funkhouser, G., Jennings, A., Mullen, S., Fowler, P., and Civil Aeromedical Institute

Abstract

The effects of a single 600-mg dose of lithium carbonate were evaluated in a study of 15 healthy, normal male subjects. Subjects were studied, on two occasions, by utilizing a double-blind design--once receiving the lithium carbonate and once receiving a lactose placebo., Measurements were made of, 1.complex performance, using the CAMI Multiple Task Performance Battery, 2.hand steadiness, using the steadiness tester of the Motor Steadiness Kit, 3.heart rate, 4.the urinary excretion of 17-ketogenic steroids, epinephrine, and norepinephrine, and, 5.short term memory, as measured by the Wechsler Memory Scale., The only statistically significant effect due to the drug was for short term memory, in which scores made by subjects taking the placebo were higher than scores made by those taking the lithium carbonate.

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