David R Williams

Harvard University, Cambridge, Massachusetts, United States

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Publications (605)2097.78 Total impact

  • David R. Williams · Paul T. Gladen · Joseph R. Pinchman ·
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    ABSTRACT: No abstract is available for this article.
    ChemInform 10/2015; 46(43). DOI:10.1002/chin.201543206
  • David R Williams · Ronald Wyatt ·

    JAMA The Journal of the American Medical Association 08/2015; 314(6):555-556. DOI:10.1001/jama.2015.9260 · 35.29 Impact Factor
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    ABSTRACT: Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P < .001) with a dark cone appearance. No foveal cones were detected in the older brother. In the younger brother, foveal cones were enlarged with low density (peak cone density, 48.3 × 103 cones/mm2). The ratio of cone to rod spacing was increased in both patients, with greater divergence from normal approaching the foveal center, indicating that cone loss predominates centrally and rod loss increases peripherally. Both parents had normal photoreceptor mosaics. Genetic testing revealed 3 disease-causing mutations. This study provides in vivo images of rods and cones in STGD1. Although the primary clinical features of STGD1 are retinal pigment epithelial lesions, adaptive optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1.
    Jama Ophthalmology 08/2015; 133(10). DOI:10.1001/jamaophthalmol.2015.2443 · 3.32 Impact Factor
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    ABSTRACT: This publisher's note amends the author list and Acknowledgments of a recent publication [Biomed. Opt. Express6, 2120 (2015)].[This corrects the article on p. 2120 in vol. 6, PMID: 26114033.].
    Biomedical Optics Express 08/2015; 6(8):2864. DOI:10.1364/BOE.6.002864 · 3.65 Impact Factor
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    ABSTRACT: Cross-cultural variability in respondent processing of survey questions may bias results from multiethnic samples. We analyzed behavior codes, which identify difficulties in the interactions of respondents and interviewers, from a discrimination module contained within a field test of the 2007 California Health Interview Survey. In all, 553 (English) telephone interviews yielded 13,999 interactions involving 22 items. Multilevel logistic regression modeling revealed that respondent age and several item characteristics (response format, customized questions, length, and first item with new response format), but not race/ethnicity, were associated with interactional problems. These findings suggest that item function within a multi-cultural, albeit English language, survey may be largely influenced by question features, as opposed to respondent characteristics such as race/ethnicity.
    International Journal of Public Opinion Research 07/2015; 27(2):244-263. DOI:10.1093/ijpor/edu024 · 1.00 Impact Factor
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    Naomi Priest · Aneez Esmail · Roger Kline · Mala Rao · Yvonne Coghill · David R Williams ·

    BMJ (online) 07/2015; 351:h3297. DOI:10.1136/bmj.h3297 · 17.45 Impact Factor
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    ABSTRACT: The total synthesis of (-)-amphidinolide K (1) based on asymmetric addition of allylsilane C1-C8 to enal C9-C22 is reported. The 1,9,18-tris-O-TBDPS-ether was converted into the desired 9,18-dihydroxyacid. Its macrolactonization was accomplished by the Shiina method under high-dilution conditions. Compound 1 together with some of its stereoisomers and analogs were subjected to evaluation of the possible disruption of the alpha,beta-tubulin-microtubule and/or G-actin-F-actin equilibria. Compound 1 behaves as a stabilizer of actin filaments (F-actin) in vitro.
    The Journal of Organic Chemistry 06/2015; 80(17). DOI:10.1021/acs.joc.5b00966 · 4.72 Impact Factor
  • Jie Zhang · Qiang Yang · Kenichi Saito · Koji Nozato · David R. Williams · Ethan A. Rossi ·
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    ABSTRACT: Here we demonstrate a new imaging system that addresses several major problems limiting the clinical utility of conventional adaptive optics scanning light ophthalmoscopy (AOSLO), including its small field of view (FOV), reliance on patient fixation for targeting imaging, and substantial post-processing time. We previously showed an efficient image based eye tracking method for real-time optical stabilization and image registration in AOSLO. However, in patients with poor fixation, eye motion causes the FOV to drift substantially, causing this approach to fail. We solve that problem here by tracking eye motion at multiple spatial scales simultaneously by optically and electronically integrating a wide FOV SLO (WFSLO) with an AOSLO. This multi-scale approach, implemented with fast tip/tilt mirrors, has a large stabilization range of ± 5.6°. Our method consists of three stages implemented in parallel: 1) coarse optical stabilization driven by a WFSLO image, 2) fine optical stabilization driven by an AOSLO image, and 3) sub-pixel digital registration of the AOSLO image. We evaluated system performance in normal eyes and diseased eyes with poor fixation. Residual image motion with incremental compensation after each stage was: 1) ~2-3 arc minutes, (arcmin) 2) ~0.5-0.8 arcmin and, 3) ~0.05-0.07 arcmin, for normal eyes. Performance in eyes with poor fixation was: 1) ~3-5 arcmin, 2) ~0.7-1.1 arcmin and 3) ~0.07-0.14 arcmin. We demonstrate that this system is capable of reducing image motion by a factor of ~400, on average. This new optical design provides additional benefits for clinical imaging, including a steering subsystem for AOSLO that can be guided by the WFSLO to target specific regions of interest such as retinal pathology and real-time averaging of registered images to eliminate image post-processing.
    Biomedical Optics Express 06/2015; 6(6):2120. DOI:10.1364/BOE.6.002120 · 3.65 Impact Factor
  • David R. Williams · Leslie A. Robinson · Seth A. Bawel ·
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    ABSTRACT: Stereoselective reactions are described which lead to functionalization of the dolabellane skeleton. The stereoselectivity is attributed to conformational effects imposed by the eleven-membered ring. An efficient pathway provides for the stereocontrolled synthesis of nonracemic 6(S)-hydroxy-4(E)-dolabellene-3-one 12 and related derivatives.
    Tetrahedron Letters 06/2015; 56(23):3200-3203. DOI:10.1016/j.tetlet.2014.12.049 · 2.38 Impact Factor
  • David R Williams · Paul T Gladen · Joseph R Pinchman ·
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    ABSTRACT: The first total synthesis of trichoaurantianolides C and D is described. An enantiocontrolled pathway leads to rapid construction of the tricyclic carbon skeleton and establishes the trans-dimethyl geometry of the quaternary bridgehead carbons via a reductive cyclization. Application of the pi-allyl Stille cross coupling leads to a nonracemic allylic alcohol as a prerequisite for the introduction of asymmetry in the cycloheptane system. Two strategies have been examined for elaboration of the unsaturated tetrahydrofuranyl ring from a common tricyclic intermediate. These efforts reveal a number of unanticipated issues of reactivity and significant stereochemical requirements for a novel acyloin rearrangement as well as the elimination and cyclodehydration of chiral alpha-hydroxyketones. Key reactions leading to completion of the synthesis include the stereoselective addition of isopropenyllithium TMEDA complex and a facile chemoselective oxidation with selenium dioxide.
    The Journal of Organic Chemistry 05/2015; 80(11). DOI:10.1021/acs.joc.5b00355 · 4.72 Impact Factor
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    ABSTRACT: We investigated Black-White differences in the association between average alcohol drinking patterns and all-cause mortality. We pooled nationally representative samples of 152 180 adults in the National Health Interview Survey from 1997 to 2002 with mortality follow-up through 2006. Usual drinking days per week and level of alcohol consumed per day were based on self-report. We used race- and gender-specific Cox proportional hazards regression analyses to adjust for physical activity, smoking status, and other potential confounders. Over 9 years, 13 366 deaths occurred from all causes. For men, the lowest multivariable-adjusted hazard ratio (HR) for total mortality among drinkers was 0.81 among White men who consumed 1 to 2 drinks 3 to 7 days per week (compared with abstainers) and Black men who abstained. For women, the lowest mortality risk was among White women (HR = 0.71) consuming 1 drink per day 3 to 7 days per week and Black women (HR = 0.72) consuming 1 drink on 2 or fewer days per week. Risks and benefits of alcohol consumption in relation to mortality risk were dependent on race- and gender-specific drinking patterns. (Am J Public Health. Published online ahead of print April 23, 2015: e1-e10. doi:10.2105/AJPH.2015.302615).
    American Journal of Public Health 04/2015; 105(S3):e1-e10. DOI:10.2105/AJPH.2015.302615 · 4.55 Impact Factor
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    ABSTRACT: In 2003, the National Cancer Institute (NCI), the National Institute of Environmental Health Sciences, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research established the Centers for Population Health and Health Disparities (CPHHD) Program in response to a strategic priority at the National Institutes of Health (NIH) to better address inequities in health among underserved racial, ethnic, and poor populations.(1) In 2009, NCI; the National Heart, Lung, and Blood Institute; and the Office of Behavioral and Social Sciences Research partnered to continue the Program. (Am J Public Health. Published online ahead of print April 23, 2015: e1-e3. doi:10.2105/AJPH.2014.302386).
    American Journal of Public Health 04/2015; 105(S3):e1-e3. DOI:10.2105/AJPH.2014.302386 · 4.55 Impact Factor
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    Loren Toussaint · Colwick M Wilson · Leon C Wilson · David R Williams ·
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    ABSTRACT: The present study examines religiousness and its connection to suicidal thoughts, plans, and attempts among Trinidad and Tobago adolescents and young adults. Data are from Trend Research Empowering National Development on adolescents and young adults in Trinidad and Tobago (N = 4448). Religious affiliation, self-perceived religiousness, attendance at religious services, prayer frequency, socio-demographic variables, and suicidal thoughts, plans, and attempts were assessed. Compared to nonreligious, Catholics (OR 0.63, p < 0.05) and Seventh-day Adventists (OR 0.47, p < 0.01) were less likely to think about suicide, and hindus (OR 5.81, p < 0.05) and other affiliates (OR 7.28, p < 0.01) were more likely to be treated for suicide. Higher self-rated religiosity was related to lower likelihood of thinking about suicide (OR 0.86, p < 0.01) and lower likelihood of planning suicide (OR 0.78, p < 0.001). Attendance at religious services was related to lower likelihood of thinking about suicide (OR 0.94, p < 05) and fewer suicide attempts (β = -0.11, p < 0.01). More frequent prayer was related to lower likelihood of thinking about suicide (OR 0.92, p < 0.01) and lower likelihood of planning suicide (OR 0.90, p < 0.001). Religiousness may offer benefits for adolescents and young adults in Trinidad and Tobago by reducing the likelihood that they engage in suicide thoughts and behaviors. Results may hold implications for counselors, clergy, teachers, and others working with adolescents and young adults in Trinidad and Tobago.
    Social Psychiatry 03/2015; 50(9). DOI:10.1007/s00127-015-1045-y · 2.54 Impact Factor
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    Lukoye Atwoli · Jonathan Platt · David R Williams · Dan J Stein · Karestan C Koenen ·
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    ABSTRACT: The high burden of witnessing traumatic events has been demonstrated in previous research in South Africa. However, previous work has focused on PTSD rather than a broader range of psychopathological outcomes. This study examined the association between witnessing trauma and multiple outcomes including mood, anxiety, and substance use disorders. Regression models measured the odds of mood, anxiety, and substance use disorders among those who reported witnessing in the South African Stress and Health Study. Discrete-time survival analysis was used to examine whether witnessing was associated with earlier onset of mental disorders. Witnessing trauma was more commonly reported among males and those with low-average education. Posttraumatic stress disorder, mood, and anxiety disorders varied significantly with witnessing status, and witnessing was associated with exposure to a higher number of traumatic events compared to other types of traumatic events. Respondents reporting witnessing trauma had elevated odds of mood and anxiety disorders, but not substance use disorders. Witnessing trauma is common in the South African population and results in increased risk of mood and anxiety disorders. Interventions aimed at reducing the burden of trauma and its outcomes must now increase their focus on bystanders and other observers, rather than just focusing on those directly affected.
    Social Psychiatry and Psychiatric Epidemiology 03/2015; 50(8). DOI:10.1007/s00127-015-1046-x · 2.54 Impact Factor
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    Julia K Boehm · Ying Chen · David R Williams · Carol Ryff · Laura D Kubzansky ·
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    ABSTRACT: Socioeconomic status is associated with health disparities, but underlying psychosocial mechanisms have not been fully identified. Dispositional optimism may be a psychosocial process linking socioeconomic status with health. We hypothesized that lower optimism would be associated with greater social disadvantage and poorer social mobility. We also investigated whether life satisfaction and positive affect showed similar patterns. Participants from the Midlife in the United States study self-reported their optimism, satisfaction, positive affect, and socioeconomic status (gender, race/ethnicity, education, occupational class and prestige, income). Social disparities in optimism were evident. Optimistic individuals tended to be white and highly educated, had an educated parent, belonged to higher occupational classes with more prestige, and had higher incomes. Findings were generally similar for satisfaction, but not positive affect. Greater optimism and satisfaction were also associated with educational achievement across generations. Optimism and life satisfaction are consistently linked with socioeconomic advantage and may be one conduit by which social disparities influence health.
    PLoS ONE 02/2015; 10(2):e0118066. DOI:10.1371/journal.pone.0118066 · 3.23 Impact Factor
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    ABSTRACT: Guided by a risk and resilience framework, the current study examined the associations between Latino adolescents' (n = 219; Mage = 14.35; SD = 1.75) perceptions of ethnic discrimination in multiple settings (e.g., online, school) and several domains of adjustment (e.g., mental health, academic), and tested whether developmentally salient cultural assets (i.e., ethnic identity) directly promoted youth adjustment or moderated the negative impact of discrimination on adjustment. Each of the 3 ethnic identity components (i.e., exploration, resolution, affirmation) demonstrated evidence of promoting positive outcomes among Latino youth; furthermore, there was some evidence that the promotive effects of affirmation and resolution were significantly stronger for older versus younger adolescents. In addition, with the exception of experiences with discrimination from adults outside of the school setting, there was evidence of ethnic identity interacting with each type of discrimination to predict Latino adolescents' self-esteem, depressive symptoms, and externalizing problems. Findings suggest directions for future research and identify potential targets for intervention that may prove fruitful in programming efforts with Latino adolescents. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Developmental Psychology 01/2015; 51(1):87-100. DOI:10.1037/a0038432 · 3.21 Impact Factor
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    ABSTRACT: Sinusoidal rectification (i.e., desinusoiding) is necessary for scanning imaging systems and is typically achieved by calculating a rectification transform from a calibration image such as a regular grid. This approach is susceptible to error due to electronic or mechanical instability that can alter the phase of the imaging window with respect to the calibration transform. Here, we show a calibration-free rectification method implemented from live video of a scanning light ophthalmoscope (SLO) with or without adaptive optics (AO). This approach, which capitalizes on positional differences in the images obtained in the forward and backward scan directions, dynamically keeps the imaging window in phase with the motion of the sinusoidal resonant scanner, preventing errors from signal drift over time. A benefit of this approach is that it allows the light power across the field-of-view (FOV) to be modulated inversely to achieve uniform irradiance on the retina, a feature desirable for functional imaging methods and light safety in SLOs.
    Optics Letters 01/2015; 40(1):85-88. DOI:10.1364/OL.40.000085 · 3.29 Impact Factor
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    ABSTRACT: Background Previous research suggests that many people receiving mental health treatment do not meet criteria for a mental disorder but are rather 'the worried well'. Aims To examine the association of past-year mental health treatment with DSM-IV disorders. Method The World Health Organization's World Mental Health (WMH) Surveys interviewed community samples of adults in 23 countries (n = 62 305) about DSM-IV disorders and treatment in the past 12 months for problems with emotions, alcohol or drugs. Results Roughly half (52%) of people who received treatment met criteria for a past-year DSM-IV disorder, an additional 18% for a lifetime disorder and an additional 13% for other indicators of need (multiple subthreshold disorders, recent stressors or suicidal behaviours). Dose-response associations were found between number of indicators of need and treatment. Conclusions The vast majority of treatment in the WMH countries goes to patients with mental disorders or other problems expected to benefit from treatment.
    The British journal of psychiatry: the journal of mental science 11/2014; 206(2). DOI:10.1192/bjp.bp.113.141424 · 7.99 Impact Factor
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    ABSTRACT: Importance The inverse social gradient in mental disorders is a well-established research finding with important implications for causal models and policy. This research has used traditional objective social status (OSS) measures, such as educational level, income, and occupation. Recently, subjective social status (SSS) measurement has been advocated to capture the perception of relative social status, but to our knowledge, there have been no studies of associations between SSS and mental disorders.Objectives To estimate associations of SSS with DSM-IV mental disorders in multiple countries and to investigate whether the associations persist after comprehensive adjustment of OSS.Design, Setting, and Participants Face-to-face cross-sectional household surveys of community-dwelling adults in 18 countries in Asia, South Pacific, the Americas, Europe, and the Middle East (N = 56 085). Subjective social status was assessed with a self-anchoring scale reflecting respondent evaluations of their place in the social hierarchies of their countries in terms of income, educational level, and occupation. Scores on the 1 to 10 SSS scale were categorized into 4 categories: low (scores 1-3), low-mid (scores 4-5), high-mid (scores 6-7), and high (scores 8-10). Objective social status was assessed with a wide range of fine-grained objective indicators of income, educational level, and occupation.Main Outcomes and Measures The Composite International Diagnostic Interview assessed the 12-month prevalence of 16 DSM-IV mood, anxiety, and impulse control disorders.Results The weighted mean survey response rate was 75.2% (range, 55.1%-97.2%). Graded inverse associations were found between SSS and all 16 mental disorders. Gross odds ratios (lowest vs highest SSS categories) in the range of 1.8 to 9.0 were attenuated but remained significant for all 16 disorders (odds ratio, 1.4-4.9) after adjusting for OSS indicators. This pattern of inverse association between SSS and mental disorders was significant in 14 of 18 individual countries, and in low-, middle-, and high-income country groups but was significantly stronger in high- vs lower-income countries.Conclusions and Relevance Significant inverse associations between SSS and numerous DSM-IV mental disorders exist across a wide range of countries even after comprehensive adjustment for OSS. Although it is unclear whether these associations are the result of social selection, social causation, or both, these results document clearly that research relying exclusively on standard OSS measures underestimates the steepness of the social gradient in mental disorders.
    JAMA Psychiatry 10/2014; 71(12). DOI:10.1001/jamapsychiatry.2014.1337 · 12.01 Impact Factor
  • Benjamin D Masella · Jennifer J Hunter · David R Williams ·
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    ABSTRACT: Purpose: Retinal densitometry provides objective information about retinal function. But, a number of factors, including retinal reflectance changes that are not directly related to photopigment depletion, complicate its interpretation. We explore these factors and suggest a method to minimize their impact. Methods: An adaptive optics scanning light ophthalmoscope (AOSLO) was used to measure changes in photoreceptor reflectance in monkeys before and after photopigment bleaching with 514-nm light. Reflectance measurements at 514 nm and 794 nm were recorded simultaneously. Several methods of normalization to extract the apparent optical density of the photopigment were compared. Results: We identified stimulus-related fluctuations in 794-nm reflectance that are not associated with photopigment absorptance and occur in both rods and cones. These changes had a magnitude approaching those associated directly with pigment depletion, precluding the use of infrared reflectance for normalization. We used a spatial normalization method instead, which avoided the fluctuations in the near infrared, as well as a confocal AOSLO designed to minimize light from layers other than the receptors. However, these methods produced a surprisingly low estimate of the apparent rhodopsin density (animal 1: 0.073 ± 0.006, animal 2: 0.032 ± 0.003). Conclusions: These results confirm earlier observations that changes in photopigment absorption are not the only source of retinal reflectance change during dark adaptation. It appears that the stray light that has historically reduced the apparent density of cone photopigment in retinal densitometry arises predominantly from layers near the photoreceptors themselves. Despite these complications, this method provides a valuable, objective measure of retinal function.
    Investigative Ophthalmology &amp Visual Science 10/2014; 55(11). DOI:10.1167/iovs.13-13795 · 3.40 Impact Factor

Publication Stats

34k Citations
2,097.78 Total Impact Points


  • 1999-2015
    • Harvard University
      • • Department of Society, Human Development, and Health
      • • Department of Psychology
      Cambridge, Massachusetts, United States
  • 1985-2015
    • University of Rochester
      • • Institute of Optics
      • • Department of Brain and Cognitive Sciences
      • • Center for Visual Science
      Rochester, New York, United States
  • 2007-2014
    • Harvard Medical School
      • • Department of Health Care Policy
      • • Department of Medicine
      Boston, Massachusetts, United States
    • The Rockefeller University
      New York, New York, United States
  • 1980-2014
    • Indiana University Bloomington
      • • Department of Chemistry
      • • Department of Physics
      Bloomington, Indiana, United States
  • 2012
    • University of Toronto
      Toronto, Ontario, Canada
    • McMaster University
      Hamilton, Ontario, Canada
  • 2007-2011
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2001-2011
    • University of California, Berkeley
      Berkeley, California, United States
    • University of Texas at Austin
      • Department of Sociology
      Austin, Texas, United States
  • 2010
    • University of Illinois, Urbana-Champaign
      Urbana, Illinois, United States
    • KU Leuven
      • Division of Psychiatry
      Leuven, VLG, Belgium
    • Columbia University
      New York City, New York, United States
  • 2009
    • Stellenbosch University
      • Department of Psychiatry
      Stellenbosch, Province of the Western Cape, South Africa
    • University of California, Davis
      Davis, California, United States
    • Union College
      New York City, New York, United States
    • DePaul University
      Chicago, Illinois, United States
  • 1994-2009
    • University of Michigan
      • • Institute for Social Research
      • • Department of Sociology
      Ann Arbor, Michigan, United States
  • 2008
    • Idenix Pharmaceuticals, Inc.
      Cambridge, Massachusetts, United States
    • East Tennessee State University
      • Department of Psychology
      جونسون سيتي، تينيسي, Tennessee, United States
    • University of Wisconsin, Madison
      • Department of Population Health Sciences
      Madison, MS, United States
  • 2005-2008
    • Yale University
      • Department of Sociology
      New Haven, CT, United States
  • 1996-2003
    • University of Murcia
      • Departamento de Física
      Murcia, Murcia, Spain
  • 2002
    • University of Houston
      • College of Optometry
      Houston, TX, United States
    • Northwestern University
      • Institute for Policy Research (IPR)
      Evanston, Illinois, United States
    • George Washington University
      • Department of Psychology
      Washington, D. C., DC, United States
    • University of California, San Francisco
      • Veterans Affairs Medical Center
      San Francisco, CA, United States
  • 1999-2002
    • Wayne State University
      • Department of Surgery
      Detroit, MI, United States
  • 1998-2002
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2000
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
  • 1991
    • University of California, Los Angeles
      • Department of Earth and Space Sciences (ESS)
      Los Ángeles, California, United States
  • 1979-1981
    • University of California, San Diego
      • Department of Psychology
      San Diego, California, United States