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P.034 Minimal symptom expression following treatment with efgartigimod in patients with Generalized Myasthenia Gravis
- Z Siddiqi, JF Howard, Jr, V Bril, T Vu, C Karam, M Pasnoor, S Muppidi, S Peric, H Murai, P Ulrichts, C T’joen, K Utsugisawa, J Verschuuren, R Mantegazza
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 50 / Issue s2 / June 2023
- Published online by Cambridge University Press:
- 05 June 2023, p. S67
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Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG levels through FcRn blockade. A key efficacy indicator in the treatment of IgG autoantibody-mediated generalized myasthenia gravis (gMG) is improvement in MG-ADL score. Methods: The ADAPT phase 3 trial evaluated safety and efficacy of efgartigimod in patients with gMG, including reaching and maintaining of minimal symptom expression (MSE; defined as an MG-ADL total score of 0 or 1). Results: 167 patients (AChR-Ab+, n=129; AChR-Ab-, n=38) were randomized to receive treatment cycles of 4 weekly infusions of efgartigimod or placebo. Significantly more AChR-Ab+ efgartigimod-treated patients achieved MSE during cycle 1 compared to placebo-treated patients (40.0% [n=26/65] vs 11.1% [n=7/63; P<0.0001]). In cycle 2, 31.4% (n=16/51) of AChR-Ab+ patients in the efgartigimod cohort achieved MSE compared to none in the placebo cohort. MG-ADL score improved by ≥6 points in 56.9% of AChR-Ab+ efgartigimod-treated patients compared to 20.6% of placebo-treated patients in cycle 1. Most patients achieved MSE by week 4 of a cycle, paralleling early reduction in IgG levels, and MSE duration ranged from 1 to ≥10 weeks. Adverse events were predominantly mild to moderate. Conclusions: Efgartigimod treatment resulted in more patients with AChR-Ab+ gMG achieving both MSE and clinically meaningful MG-ADL improvements.
P.043 Long-term safety, tolerability, and efficacy of efgartigimod in patients with Generalized Myasthenia Gravis: concluding analyses from ADAPT+
- A Genge, M Pasnoor, V Bril, C Karam, S Peric, JL De Bleecker, H Murai, A Meisel, S Beydoun, T Vu, P Ulrichts, B Van Hoorick, C T’joen, K Utsugisawa, J Verschuuren, R Mantegazza, JF Howard, Jr
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 50 / Issue s2 / June 2023
- Published online by Cambridge University Press:
- 05 June 2023, p. S69
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Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 mg/kg intravenous) was administered in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. ADAPT+ evaluated long-term safety and tolerability of efgartigimod in patients with gMG. Efficacy was assessed utilizing MG-ADL and QMG scores. Results: Of 167 patients from ADAPT, 151 (90%) entered ADAPT+, and 145 received ≥1 cycle as of January 2022. Over 217.55 patient-years of follow-up (mean duration per patient, 548 days), incidence of adverse events did not increase with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. All AChR-Ab+ patients (n=111) demonstrated consistent improvements (mean change [SE], week 3 of cycle 1) in MG-ADL (-5.0 [0.33]; up to 14 cycles) and QMG (-4.7 [0.41]; up to 7 cycles) scores during each cycle. Conclusions: These ADAPT+ analyses suggest long-term efgartigimod treatment is well tolerated and efficacious. Additional final data cut analyses will be presented at CNSF 2023.
Examining associations between genetic and neural risk for externalizing behaviors in adolescence and early adulthood
- Sarah J. Brislin, Jessica E. Salvatore, Jacquelyn M. Meyers, Chella Kamarajan, Martin H. Plawecki, Howard J. Edenberg, Samuel Kuperman, Jay Tischfield, Victor Hesselbrock, Andrey P. Anokhin, David B. Chorlian, Marc A. Schuckit, John I. Nurnberger, Jr., Lance Bauer, Gayathri Pandey, Ashwini K. Pandey, John R. Kramer, Grace Chan, Bernice Porjesz, COGA Collaborators, Danielle M. Dick
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 19 May 2023, pp. 267-277
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Background
Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.
MethodsParticipants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).
ResultsThe EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.
ConclusionsBoth the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.
418 Activation of the Glucagon-Like Peptide-1 Pathway in Obese Pre-Diabetic Individuals Improves Endothelial Function Independently of Weight Loss
- Mona Mashayekhi, Joshua A. Beckman, Erica M. Garner, Hui Nian, Chang Yu, Sara E. Howard, Bradley Perkins, Jessica K. Devin, John R. Koethe, Jonathan D. Brown, Heidi Silver, James M. Luther, Nancy J. Brown
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, pp. 81-82
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OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
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- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
- Emma C. Johnson, Manav Kapoor, Alexander S. Hatoum, Hang Zhou, Renato Polimanti, Frank R. Wendt, Raymond K. Walters, Dongbing Lai, Rachel L. Kember, Sarah Hartz, Jacquelyn L. Meyers, Roseann E. Peterson, Stephan Ripke, Tim B. Bigdeli, Ayman H. Fanous, Carlos N. Pato, Michele T. Pato, Alison M. Goate, Henry R. Kranzler, Michael C. O'Donovan, James T.R. Walters, Joel Gelernter, Howard J. Edenberg, Arpana Agrawal
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- Psychological Medicine / Volume 53 / Issue 4 / March 2023
- Published online by Cambridge University Press:
- 07 July 2021, pp. 1196-1204
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Background
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
MethodsWe used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
ResultsWe identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
ConclusionsOur findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Neutron Star Extreme Matter Observatory: A kilohertz-band gravitational-wave detector in the global network
- Part of
- K. Ackley, V. B. Adya, P. Agrawal, P. Altin, G. Ashton, M. Bailes, E. Baltinas, A. Barbuio, D. Beniwal, C. Blair, D. Blair, G. N. Bolingbroke, V. Bossilkov, S. Shachar Boublil, D. D. Brown, B. J. Burridge, J. Calderon Bustillo, J. Cameron, H. Tuong Cao, J. B. Carlin, S. Chang, P. Charlton, C. Chatterjee, D. Chattopadhyay, X. Chen, J. Chi, J. Chow, Q. Chu, A. Ciobanu, T. Clarke, P. Clearwater, J. Cooke, D. Coward, H. Crisp, R. J. Dattatri, A. T. Deller, D. A. Dobie, L. Dunn, P. J. Easter, J. Eichholz, R. Evans, C. Flynn, G. Foran, P. Forsyth, Y. Gai, S. Galaudage, D. K. Galloway, B. Gendre, B. Goncharov, S. Goode, D. Gozzard, B. Grace, A. W. Graham, A. Heger, F. Hernandez Vivanco, R. Hirai, N. A. Holland, Z. J. Holmes, E. Howard, E. Howell, G. Howitt, M. T. Hübner, J. Hurley, C. Ingram, V. Jaberian Hamedan, K. Jenner, L. Ju, D. P. Kapasi, T. Kaur, N. Kijbunchoo, M. Kovalam, R. Kumar Choudhary, P. D. Lasky, M. Y. M. Lau, J. Leung, J. Liu, K. Loh, A. Mailvagan, I. Mandel, J. J. McCann, D. E. McClelland, K. McKenzie, D. McManus, T. McRae, A. Melatos, P. Meyers, H. Middleton, M. T. Miles, M. Millhouse, Y. Lun Mong, B. Mueller, J. Munch, J. Musiov, S. Muusse, R. S. Nathan, Y. Naveh, C. Neijssel, B. Neil, S. W. S. Ng, V. Oloworaran, D. J. Ottaway, M. Page, J. Pan, M. Pathak, E. Payne, J. Powell, J. Pritchard, E. Puckridge, A. Raidani, V. Rallabhandi, D. Reardon, J. A. Riley, L. Roberts, I. M. Romero-Shaw, T. J. Roocke, G. Rowell, N. Sahu, N. Sarin, L. Sarre, H. Sattari, M. Schiworski, S. M. Scott, R. Sengar, D. Shaddock, R. Shannon, J. SHI, P. Sibley, B. J. J. Slagmolen, T. Slaven-Blair, R. J. E. Smith, J. Spollard, L. Steed, L. Strang, H. Sun, A. Sunderland, S. Suvorova, C. Talbot, E. Thrane, D. Töyrä, P. Trahanas, A. Vajpeyi, J. V. van Heijningen, A. F. Vargas, P. J. Veitch, A. Vigna-Gomez, A. Wade, K. Walker, Z. Wang, R. L. Ward, K. Ward, S. Webb, L. Wen, K. Wette, R. Wilcox, J. Winterflood, C. Wolf, B. Wu, M. Jet Yap, Z. You, H. Yu, J. Zhang, J. Zhang, C. Zhao, X. Zhu
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 37 / 2020
- Published online by Cambridge University Press:
- 05 November 2020, e047
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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Overview of the SPARC tokamak
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- A. J. Creely, M. J. Greenwald, S. B. Ballinger, D. Brunner, J. Canik, J. Doody, T. Fülöp, D. T. Garnier, R. Granetz, T. K. Gray, C. Holland, N. T. Howard, J. W. Hughes, J. H. Irby, V. A. Izzo, G. J. Kramer, A. Q. Kuang, B. LaBombard, Y. Lin, B. Lipschultz, N. C. Logan, J. D. Lore, E. S. Marmar, K. Montes, R. T. Mumgaard, C. Paz-Soldan, C. Rea, M. L. Reinke, P. Rodriguez-Fernandez, K. Särkimäki, F. Sciortino, S. D. Scott, A. Snicker, P. B. Snyder, B. N. Sorbom, R. Sweeney, R. A. Tinguely, E. A. Tolman, M. Umansky, O. Vallhagen, J. Varje, D. G. Whyte, J. C. Wright, S. J. Wukitch, J. Zhu, the SPARC Team
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- Journal:
- Journal of Plasma Physics / Volume 86 / Issue 5 / October 2020
- Published online by Cambridge University Press:
- 29 September 2020, 865860502
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The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
A Jeolco 200A Cartridge with Specimen Heating, Tilting, and Power Provisions
- R. M. Anderson, J. K. Howard, P. Fullam
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- Journal:
- Proceedings, annual meeting, Electron Microscopy Society of America / Volume 33 / 15 1975
- Published online by Cambridge University Press:
- 18 June 2020, pp. 152-153
- Print publication:
- 15 1975
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The transmission electron microscopic study of thin metal film interconnections on electronic integrated circuits requires a sophisticated in-situ capability. Electromigration, particularly, cannot be investigated solely by viewing static heat-treated or electrically stressed specimens ex-situ. The key to the early electromigration studies by Blech, and others, was the in-situ observation of material movement in anelectrical-powering-stage equipped TEM. Blech's approach was insensitive to structure effects because of an absence of heating capability; he therefore relied on joule heating and temperature gradient effects.
Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples
- Emma C. Johnson, Sandra Sanchez-Roige, Laura Acion, Mark J. Adams, Kathleen K. Bucholz, Grace Chan, Michael J. Chao, David B. Chorlian, Danielle M. Dick, Howard J. Edenberg, Tatiana Foroud, Caroline Hayward, Jon Heron, Victor Hesselbrock, Matthew Hickman, Kenneth S. Kendler, Sivan Kinreich, John Kramer, Sally I-Chun Kuo, Samuel Kuperman, Dongbing Lai, Andrew M. McIntosh, Jacquelyn L. Meyers, Martin H. Plawecki, Bernice Porjesz, David Porteous, Marc A. Schuckit, Jinni Su, Yong Zang, Abraham A. Palmer, Arpana Agrawal, Toni-Kim Clarke, Alexis C. Edwards
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- Psychological Medicine / Volume 51 / Issue 7 / May 2021
- Published online by Cambridge University Press:
- 20 January 2020, pp. 1147-1156
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Background
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
MethodsWe examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
ResultsIn COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
ConclusionsAUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Amorphous and Nano-Crystalline Materials in Pristine Carbonaceous Chondrite Meteorites
- Neyda M. Abreu, C. M. Corrigan, D. C. Hezel, L. P. Keller, K. T. Howard, B. T. De Gregorio, K. L. Crispin, J. Gray, H. Wang
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- Journal:
- Microscopy and Microanalysis / Volume 25 / Issue S2 / August 2019
- Published online by Cambridge University Press:
- 05 August 2019, pp. 2452-2453
- Print publication:
- August 2019
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A One Health investigation of Salmonella enterica serovar Wangata in north-eastern New South Wales, Australia, 2016–2017
- J. Collins, K. M. J. Simpson, G. Bell, D. N. Durrheim, G. A. Hill-Cawthorne, K. Hope, P. Howard, T. Kohlenberg, K. Lawrence, K. Lilly, P. Porigneaux, V. Sintchenko, Q. Wang, M. P. Ward, A. Wiethoelter, S. M. Mor, J. Flint
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- Journal:
- Epidemiology & Infection / Volume 147 / 2019
- Published online by Cambridge University Press:
- 12 March 2019, e150
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Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.
Understanding Mechanisms of Genetic Risk for Adolescent Internalizing and Externalizing Problems: The Mediating Role of Parenting and Personality
- Jinni Su, Sally I-Chun Kuo, Kathleen K. Bucholz, Howard J. Edenberg, John R. Kramer, Marc Schuckit, Danielle M. Dick
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- Journal:
- Twin Research and Human Genetics / Volume 21 / Issue 4 / August 2018
- Published online by Cambridge University Press:
- 20 July 2018, pp. 310-321
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Genetic predispositions play an important role in the development of internalizing and externalizing behaviors. Understanding the mechanisms through which genetic risk unfolds to influence these developmental outcomes is critical for developing prevention and intervention efforts, capturing key elements of Irv's research agenda and scientific legacy. In this study, we examined the role of parenting and personality in mediating the effect of genetic risk on adolescents’ major depressive disorder and conduct disorder symptoms. Longitudinal data were drawn from a sample of 709 European American adolescents and their mothers from the Collaborative Studies on Genetics of Alcoholism. Results from multivariate path analysis indicated that adolescents’ depressive symptoms genome-wide polygenic scores (DS_GPS) predicted lower parental knowledge, which in turn was associated with more subsequent major depressive disorder and conduct disorder symptoms. Adolescents’ DS_GPS also had indirect effects on these outcomes via personality, with a mediating effect via agreeableness but not via other dimensions of personality. Findings revealed that the pattern of associations was similar across adolescent gender. Our findings emphasize the important role of evocative gene–environment correlation processes and intermediate phenotypes in the pathways of risk from genetic predispositions to complex adolescent outcomes.
22 - Understanding Couple Conflict
- from Part VI - Interactive Processes
- Edited by Anita L. Vangelisti, University of Texas, Austin, Daniel Perlman, University of North Carolina, Greensboro
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- The Cambridge Handbook of Personal Relationships
- Published online:
- 11 June 2018
- Print publication:
- 21 June 2018, pp 297-310
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Summary
This chapter covers past and present research on romantic love, with an emphasis on recent scholarship in this area. We begin with an overview of definitions and theories of romantic love, continue with a focus on the biological basis of love (including several recent fMRI studies), and finish with an emphasis on maintaining long-term romantic love. We consider research on romantic love from a variety of theoretical perspectives including cross-cultural models, attachment theoretical approaches, evolutionary models, and in light of the self-expansion model. In addition, we consider the dark side of love, which can result in a variety of emotional responses and can potentially lead to loss of self. We also suggest fruitful areas for future research, including the effects of falling in love on the self, the processes and motivations associated with unrequited love, and the course of passionate love over time including potential moderators of that course. All work in this area converges on the idea that romantic love is an essential human experience that is worthy of future study. Though much progress has been made, there is still much to be done.
Evaluation of data accuracies within a comprehensive geospatial-health data surveillance platform: SOMAARTH Demographic Development and Environmental Surveillance Site, Palwal, Haryana, India
- Natasha J. Howard, Shikha Dixit, Hasan Raja Naqvi, Atiqur Rahman, Catherine Paquet, Mark Daniel, Narendra K. Arora
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- Journal:
- Global Health, Epidemiology and Genomics / Volume 3 / 2018
- Published online by Cambridge University Press:
- 27 December 2018, e19
- Print publication:
- 2018
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Evidence exists of an increasing prevalence of chronic conditions within developed and developing nations, notably for priority population groups. The need for the collection of geospatial data to monitor the health impact of rapid social-environmental and economic changes occurring in these countries is being increasingly recognized. Rigorous accuracy assessment of such geospatial data is required to enable error estimation, and ultimately, data utility for exploring population health. This research outlines findings from a field-based evaluation exercise of the SOMAARTH DDESS geospatial-health platform. Participatory-based mixed methods have been employed within Palwal-India to capture villager perspectives on built infrastructure across 51 villages. This study, conducted in 2013, included an assessment of data element position and attribute accuracy undertaken in six villages, documenting mapping errors and land parcel changes. Descriptive analyses of 5.1% (n = 455) of land parcels highlighted some discrepancies in position (6.4%) and attribute (4.2%) accuracy, and land parcel changes (17.4%). Furthermore, the evaluation led to a refinement of the existing geospatial health platform incorporating ground-truthed reflections from the participatory field exercise. The evaluation of geospatial data accuracies contributes to understandings on global public health surveillance systems, outlining the need to systematically consider assessment of environmental features in relation to lifestyle-related diseases.
Key patterns and predictors of response to treatment for military veterans with post-traumatic stress disorder: a growth mixture modelling approach
- A. J. Phelps, Z. Steel, O. Metcalf, N. Alkemade, K. Kerr, M. O'Donnell, J. Nursey, J. Cooper, A. Howard, R. Armstrong, D. Forbes
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- Journal:
- Psychological Medicine / Volume 48 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 15 November 2017, pp. 95-103
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Background
To determine the patterns and predictors of treatment response trajectories for veterans with post-traumatic stress disorder (PTSD).
MethodsConditional latent growth mixture modelling was used to identify classes and predictors of class membership. In total, 2686 veterans treated for PTSD between 2002 and 2015 across 14 hospitals in Australia completed the PTSD Checklist at intake, discharge, and 3 and 9 months follow-up. Predictor variables included co-morbid mental health problems, relationship functioning, employment and compensation status.
ResultsFive distinct classes were found: those with the most severe PTSD at intake separated into a relatively large class (32.5%) with small change, and a small class (3%) with a large change. Those with slightly less severe PTSD separated into one class comprising 49.9% of the total sample with large change effects, and a second class comprising 7.9% with extremely large treatment effects. The final class (6.7%) with least severe PTSD at intake also showed a large treatment effect. Of the multiple predictor variables, depression and guilt were the only two found to predict differences in response trajectories.
ConclusionsThese findings highlight the importance of assessing guilt and depression prior to treatment for PTSD, and for severe cases with co-morbid guilt and depression, considering an approach to trauma-focused therapy that specifically targets guilt and depression-related cognitions.
Epidemiology and whole genome sequencing of an ongoing point-source Salmonella Agona outbreak associated with sushi consumption in western Sydney, Australia 2015
- C. K. THOMPSON, Q. WANG, S. K. BAG, N. FRANKLIN, C. T. SHADBOLT, P. HOWARD, E. J. FEARNLEY, H. E. QUINN, V. SINTCHENKO, K. G. HOPE
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- Journal:
- Epidemiology & Infection / Volume 145 / Issue 10 / July 2017
- Published online by Cambridge University Press:
- 02 May 2017, pp. 2062-2071
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During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.
An outbreak of Shiga toxin-producing Escherichia coli serogroup O157 linked to a lamb-feeding event
- S. ROWELL, C. KING, C. JENKINS, T. J. DALLMAN, V. DECRAENE, K. LAMDEN, A. HOWARD, C. A. FEATHERSTONE, P. CLEARY
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- Journal:
- Epidemiology & Infection / Volume 144 / Issue 12 / September 2016
- Published online by Cambridge University Press:
- 14 June 2016, pp. 2494-2500
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Fifteen confirmed cases and 15 possible cases of Shiga toxin-producing Escherichia coli (STEC) O157 phage type 21/28 were linked to direct contact with lambs at a ‘Lambing Live’ event in the North West of England between 29 March and 21 April 2014. Twenty-one (70%) of the cases were female, 23 (77%) were children aged <16 years, of whom 14 (46%) were in the 0–5 years age group. Five children developed haemolytic uraemic syndrome. Multilocus variable number tandem repeat analysis (MLVA) profiles on 14 human cases were indistinguishable, and 6/10 animal isolates had a MLVA profile identical to the outbreak profile. Whole-genome sequencing analysis revealed that all isolates, both human and animal, fell within a 5-single nucleotide polymorphism cluster indicating the isolates belonged to the same point source. On inspection of the premises, extensive and uncontrolled physical contact between visitors and animals was occuring within the animal pens and during bottle-feeding. Public areas were visibly contaminated with animal faeces. Information to visitors, and the infection control awareness demonstrated by staff, was inadequate. Managing the risk to visitors of STEC O157 infection at animal petting events and open farms requires implementation of stringent control measures by the operator, as outlined in the industry code of practice. Enforcement action is sometimes required to prevent high-risk activities taking place at both permanent and temporary attractions.
Notes on contributors
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- By Margaret Bent, Anna Maria Busse Berger, Lawrence F. Bernstein, Bonnie J. Blackburn, M. Jennifer Bloxam, Philippe Canguilhem, Julie E. Cumming, Anthony M. Cummings, David Fallows, David Fiala, Alison K. Frazier, James Hankins, Leofranc Holford-Strevens, Deborah Howard, Andrew Kirkman, Michael Long, Laurenz Lütteken, Evan A. MacCarthy, Patrick Macey, Honey Meconi, John Milsom, Klaus Pietschmann, Alejandro Enrique Planchart, Yolanda Plumley, Keith Polk, Anne Walters Robertson, Jesse Rodin, David J. Rothenberg, Thomas Schmidt-Beste, Peter Schubert, Nicole Schwindt, Richard Sherr, Pamela F. Starr, Anne Stone, Reinhard Strohm, Richard Taruskin, Blake Wilson, Emily Zazulia
- Edited by Anna Maria Busse Berger, University of California, Davis, Jesse Rodin, Stanford University, California
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- Book:
- The Cambridge History of Fifteenth-Century Music
- Published online:
- 05 July 2015
- Print publication:
- 16 July 2015, pp xix-xxvi
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Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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