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4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 527-528
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Objective:
Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
Dynamics and risk of transmission of bovine tuberculosis in the emerging dairy regions of Ethiopia
- G. A. Mekonnen, A. J. K. Conlan, S. Berg, B. T. Ayele, A. Mihret, A. Olani, H. Asgedom, The ETHICOBOTS consortium , J. L. N. Wood, G. Ameni
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- Journal:
- Epidemiology & Infection / Volume 149 / 2021
- Published online by Cambridge University Press:
- 24 February 2021, e69
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The Ethiopian government has several initiatives to expand and intensify the dairy industry; however, the risk of bovine tuberculosis (bTB) spread is a challenge. To assess the rate of expansion and risk factors for transmission of bTB within-herds, we carried out a repeated cross-sectional survey at two time points, 2016/17 and 2018, in three regional cities, namely, Gondar, Hawassa and Mekelle, representing the emerging dairy belts of Ethiopia. The total number of herds involved was 128, comprising an average of 2303 cattle in each round. The Single Intradermal Comparative Cervical Tuberculin (SICCT) test was used to identify reactor status and data on herd-level risk factors were collected using a structured questionnaire. In the first survey, the apparent prevalence of bTB, as measured by the SICCT test, was 4.5% (95% CI 3.7–5.4%) at the individual animal-level and 24% (95% CI 17.5–32%) at the herd-level. There was no statistically significant change in the overall apparent prevalence or regional distribution at the second survey, consistent with the infection being endemic. The incidence rate was estimated at 3.6 (95% CI 2.8–4.5) and 6.6 (95% CI 3.0–12.6) cases/100 cattle (or herd)-years at the animal- and herd-levels, respectively. Risk factors significantly associated with the within-herd transmission of bTB were age group and within-herd apparent prevalence at the start of the observation period. We noted that farmers voluntarily took steps to remove reactor cattle from their herds as a consequence of the information shared after the first survey. Removal of reactors between surveys was associated with a reduced risk of transmission within these herds. However, with no regulatory barriers to the sale of reactor animals, such actions could potentially lead to further spread between herds. We therefore advocate the importance of setting up regulations and then establishing a systematic bTB surveillance programme to monitor the impact prior to implementing any control measures in Ethiopia.
Dysphagia presentation and management following coronavirus disease 2019: an acute care tertiary centre experience
- Part of
- C Dawson, R Capewell, S Ellis, S Matthews, S Adamson, M Wood, L Fitch, K Reid, M Shaw, J Wheeler, P Pracy, P Nankivell, N Sharma
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- Journal:
- The Journal of Laryngology & Otology / Volume 134 / Issue 11 / November 2020
- Published online by Cambridge University Press:
- 10 November 2020, pp. 981-986
- Print publication:
- November 2020
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Objectives
As the pathophysiology of Covid-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital.
ResultsDuring the first wave of the Covid-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status.
ConclusionDysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with Covid-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.
EPA-1671 – Diagnosing Schizophrenia Using Neuroimaging: A Meta-analysis of Multivariate Pattern Recognition Studies
- J. Kambeitz, L. Kambeitz-Ilankovic, S. Leucht, S. Wood, C. Davatzikos, B. Malchow, P. Falkai, N. Koutsouleris
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- European Psychiatry / Volume 29 / Issue S1 / 2014
- Published online by Cambridge University Press:
- 15 April 2020, pp. 1-2
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Background
Numerous studies have applied novel multivariate statistical approaches to the analysis of brain alterations in patients with schizophrenia. However the diagnostic accuracy of the reported predictive models differs largely, making it difficult to evaluate the overall potential of these studies to inform clinical diagnosis.
MethodsWe conducted a comprehensive literature search to identify all studies reporting performance of neuroimaging-based multivariate predictive models for the differentiation of patients with schizophrenia from healthy control subjects. The robustness of the results as well as the effect of potentially confounding continous variables (e.g. age, gender ratio, year of publication) was investigated.
ResultsThe final sample consisted of n=37 studies studies including n=1491 patients with schizophrenia and n=1488 healthy controls. Metaanalysis of the complete sample showed a sensitivity of 80.7% (95%-CI: 77.0 to 83.9%) and a specificity of 80.2% (95%-CI: 83.3 to 76.7%). Separate analysis for the different imaging modalities showed similar diagnostic accuracy for the structural MRI studies (sensitivity 77.3%, specificity 78.7%), the fMRI studies (sensitivity 81.4%, specificity 82.4%) and resting-state fMRI studies (sensitivity 86.9%, specificity 80.3%). Moderator analysis showed significant effects of age of patients on sensitivity (p=0.021) and of positive-tonegative symptom ratio on specificity (p=0.028) indicating better diagnostic accuracy in older patients and patients with positive symptoms.
DiscussionOur analysis indicate an overall sensitivity and overall specificity of around 80 % of neuroimaging-based predictive models for differentiating schizophrenic patients from healthy controls. The results underline the potential applicability of neuroimaging-based predictive models for the diagnosis of schizophrenia.
Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function
- Jiayi Xu, Traci M. Bartz, Geetha Chittoor, Gudny Eiriksdottir, Ani W. Manichaikul, Fangui Sun, Natalie Terzikhan, Xia Zhou, Sarah L. Booth, Guy G. Brusselle, Ian H. de Boer, Myriam Fornage, Alexis C. Frazier-Wood, Mariaelisa Graff, Vilmundur Gudnason, Tamara B. Harris, Albert Hofman, Ruixue Hou, Denise K. Houston, David R. Jacobs, Jr, Stephen B. Kritchevsky, Jeanne Latourelle, Rozenn N. Lemaitre, Pamela L. Lutsey, George O’Connor, Elizabeth C. Oelsner, James S. Pankow, Bruce M. Psaty, Rebecca R. Rohde, Stephen S. Rich, Jerome I. Rotter, Lewis J. Smith, Bruno H. Stricker, V. Saroja Voruganti, Thomas J. Wang, M. Carola Zillikens, R. Graham Barr, Josée Dupuis, Sina A. Gharib, Lies Lahousse, Stephanie J. London, Kari E. North, Albert V. Smith, Lyn M. Steffen, Dana B. Hancock, Patricia A. Cassano
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- Journal:
- British Journal of Nutrition / Volume 120 / Issue 10 / 28 November 2018
- Published online by Cambridge University Press:
- 12 September 2018, pp. 1159-1170
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- 28 November 2018
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The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Relative impact of early versus late design decisions in systems development
- James J. Y. Tan, Kevin N. Otto, Kristin L. Wood
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- Design Science / Volume 3 / 2017
- Published online by Cambridge University Press:
- 08 August 2017, e12
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To better understand the impact of early versus late design decisions, a study was undertaken on the root causes of missed requirements in new product development and their impact on development cost through rework activities. The context is the industrial development of unmanned aerial vehicles. The aim is to understand the occurrence rate of missed requirements, their root causes, and their relative impact. A quantitative approach of counting requirements changes and using engineering documentation enabled traceability from observation back to root cause origin. The development process was partitioned into sequential program segments, to categorize activities to before and after concept and design freeze. We found that there was a significant difference in the rate of design defects arising before and after concept freeze; and found there was a significantly higher number of corrective activities required for design defects arising earlier before concept freeze. The revision rate of concept phase decisions was over 50%, and the rework multiplier if detected late was over 10X. In combination, design decisions made before design freeze accounted for 86% of the total expected program cost, and 34% was determined before concept freeze. These results quantify and support the anecdotal 80–20 impact rule for design decisions.
Legionella longbeachae detected in an industrial cooling tower linked to a legionellosis outbreak, New Zealand, 2015; possible waterborne transmission?
- C. N. THORNLEY, D. J. HARTE, R. P. WEIR, L. J. ALLEN, K. J. KNIGHTBRIDGE, P. R. T. WOOD
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- Journal:
- Epidemiology & Infection / Volume 145 / Issue 11 / August 2017
- Published online by Cambridge University Press:
- 19 June 2017, pp. 2382-2389
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A legionellosis outbreak at an industrial site was investigated to identify and control the source. Cases were identified from disease notifications, workplace illness records, and from clinicians. Cases were interviewed for symptoms and risk factors and tested for legionellosis. Implicated environmental sources were sampled and tested for legionella. We identified six cases with Legionnaires’ disease and seven with Pontiac fever; all had been exposed to aerosols from the cooling towers on the site. Nine cases had evidence of infection with either Legionella pneumophila serogroup (sg) 1 or Legionella longbeachae sg1; these organisms were also isolated from the cooling towers. There was 100% DNA sequence homology between cooling tower and clinical isolates of L. pneumophila sg1 using sequence-based typing analysis; no clinical L. longbeachae isolates were available to compare with environmental isolates. Routine monitoring of the towers prior to the outbreak failed to detect any legionella. Data from this outbreak indicate that L. pneumophila sg1 transmission occurred from the cooling towers; in addition, L. longbeachae transmission was suggested but remains unproven. L. longbeachae detection in cooling towers has not been previously reported in association with legionellosis outbreaks. Waterborne transmission should not be discounted in investigations for the source of L. longbeachae infection.
Delivering 21st century Antarctic and Southern Ocean science
- M.C. Kennicutt II, Y.D. Kim, M. Rogan-Finnemore, S. Anandakrishnan, S.L. Chown, S. Colwell, D. Cowan, C. Escutia, Y. Frenot, J. Hall, D. Liggett, A.J. Mcdonald, U. Nixdorf, M.J. Siegert, J. Storey, A. Wåhlin, A. Weatherwax, G.S. Wilson, T. Wilson, R. Wooding, S. Ackley, N. Biebow, D. Blankenship, S. Bo, J. Baeseman, C.A. Cárdenas, J. Cassano, C. Danhong, J. Dañobeitia, J. Francis, J. Guldahl, G. Hashida, L. Jiménez Corbalán, A. Klepikov, J. Lee, M. Leppe, F. Lijun, J. López-Martinez, M. Memolli, Y. Motoyoshi, R. Mousalle Bueno, J. Negrete, M.A. Ojeda Cárdenes, M. Proaño Silva, S. Ramos-Garcia, H. Sala, H. Shin, X. Shijie, K. Shiraishi, T. Stockings, S. Trotter, D.G. Vaughan, J. Viera Da Unha De Menezes, V. Vlasich, Q. Weijia, J.-G. Winther, H. Miller, S. Rintoul, H. Yang
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- Journal:
- Antarctic Science / Volume 28 / Issue 6 / December 2016
- Published online by Cambridge University Press:
- 21 October 2016, pp. 407-423
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The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
Aerodynamic characteristics of low-drag bicycle wheels
- D. I. Greenwell, N. J. Wood, E. K. L. Bridge, R. J. Addy
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- Journal:
- The Aeronautical Journal / Volume 99 / Issue 983 / March 1995
- Published online by Cambridge University Press:
- 04 July 2016, pp. 109-120
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A number of modern “aerodynamic” bicycle wheels were tested at full scale speeds in a windtunnel. The effects of wheel geometry, rotational speed and cross winds on drag force, side force and yawing moment were investigated.
Compared with a conventional spoked wheel, all the “aerodynamic” wheels were found to give similar improvements in drag of approximately 25%. In cross wind conditions, aerodynamic characteristics were strongly dependent on wheel geometry, but essentially independent of wheel rotational speed.
Dye visualisation of inclined and skewed synthetic jets in a cross flow
- S. Zhong, L. Garcillan, N. J Wood
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- The Aeronautical Journal / Volume 109 / Issue 1093 / March 2005
- Published online by Cambridge University Press:
- 03 February 2016, pp. 147-155
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Dye visualisation of both inclined synthetic jets and skewed synthetic jets was undertaken in a cross-flow experiment and the results were compared with those of normal synthetic jets. The process of vortex roll-up near the orifice exit and how the structure develops and interacts with the cross-flow as it propagates downstream was investigated so as to obtain an understanding of the effect of orifice orientation on the behaviour of synthetic jets. The effects of varying Reynolds number, velocity ratio and Strouhal number due to changes in diaphragm displacements and freestream velocities on the characteristics of synthetic jets were also examined. It is observed that in comparison to the normal jets vortical structures produced by both inclined and skewed jets tend to stay closer to the near wall region where maximum flow control effect is required. In both cases, at a relatively low Reynolds number and velocity ratio the active structures produced by the synthetic jet appear to be hairpin vortices which turn into vortex rings that migrate away from the wall as the Reynolds number and velocity ratio increase. These hairpin vortices are persistent in the near wall region hence are believed to be desirable structures for delaying flow separation.
Polygenic interactions with environmental adversity in the aetiology of major depressive disorder
- N. Mullins, R. A. Power, H. L. Fisher, K. B. Hanscombe, J. Euesden, R. Iniesta, D. F. Levinson, M. M. Weissman, J. B. Potash, J. Shi, R. Uher, S. Cohen-Woods, M. Rivera, L. Jones, I. Jones, N. Craddock, M. J. Owen, A. Korszun, I. W. Craig, A. E. Farmer, P. McGuffin, G. Breen, C. M. Lewis
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- Journal:
- Psychological Medicine / Volume 46 / Issue 4 / March 2016
- Published online by Cambridge University Press:
- 03 November 2015, pp. 759-770
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Background
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
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. 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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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- The Cambridge Dictionary of Philosophy
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- 05 August 2015
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- 27 April 2015, pp ix-xxx
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- By Zachary W. Adams, Margarita Alegría, Atalay Alem, Jordi Alonso, Victor Aparicio, Rifat Atun, Florence Baingana, Emily Baron, Marco Bertelli, Dinesh Bhugra, Sanchita Biswas, José Miguel Caldas de Almeida, Edwin Cameron, Somnath Chatterji, Erminia Colucci, Janice L. Cooper, Carla Kmett Danielson, Diego De Leo, Mary-Jo DelVecchio Good, Marten W. de Vries, Maureen S. Durkin, Xiangming Fang, Julia W. Felton, Sally Field, Andrea Fiorillo, Lance Gable, Teddy Gafna, Sandro Galea, Patrick Gatonga, Sofia Halperin-Goldstein, Yanling He, Grace A. Herbert, Sabrina Hermosilla, Simone Honikman, Takashi Izutsu, Ruwan M. Jayatunge, Janis H. Jenkins, Rachel Jenkins, Lynne Jones, Jayanthi Karunaratne, Ronald C. Kessler, Rob Keukens, Lincoln I. Khasakhala, Hanna Kienzler, Sarah Kippen Wood, M. Thomas Kishore, Robert Kohn, Natasja Koitzsch Jensen, Sheri Lapatin, Anna Lessios, Isabel Louro Bernal, Feijun Luo, Laura MacPherson, Matthew J. Maenner, Anne W. Mbwayo, David McDaid, Ingrid Meintjes, Victoria N. Mutiso, David M. Ndetei, Samuel O. Okpaku, Lijing Ouyang, Ramachandran Padmavati, Clare Pain, Duncan Pedersen, Jordan Pfau, Felipe Picon, Rodney D. Presley, Reima Pryor, Shoba Raja, Thara Rangaswamy, Jorge Rodriguez, Diana Rose, Moosa Salie, Norman Sartorius, Ester Shapiro, Manuela Silva, Daya Somasundaram, Katherine Sorsdahl, Dan J. Stein, Deborah M. Stone, Heather Stuart, Athula Sumathipala, Hema Tharoor, Rita Thom, Lay San Too, Atsuro Tsutsumi, Chris Underhill, Anne Valentine, Claire van der Westhuizen, Thandi van Heyningen, Robert van Voren, Inka Weissbecker, Gail Wyatt
- Edited by Samuel O. Okpaku
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- Essentials of Global Mental Health
- Published online:
- 05 March 2014
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- 27 February 2014, pp x-xiv
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- By Syed S. Ali, Nathan Allen, John E. Arbo, Elizabeth Arrington, Ani Aydin, Kenneth R. L. Bernard, Amy Caggiula, Nolan Caldwell, Jennifer L. Carey, Jennifer Carnell, Jayaram Chelluri, Michael N. Cocchi, Cristal Cristia, Vishal Demla, Bram Dolcourt, Andrew Eyre, Shawn Fagan, Brandy Ferguson, Sarah Fisher, Jonathan Friedstat, Brian C. Geyer, Brandon Godbout, Jeremy Gonda, Jeremy Goverman, Ashley L. Greiner, Casey Grover, Carla Haack, Abigail Hankin, John W. Hardin, Katrina L. Harper, Gregory Hayward, Stephen Hendriksen, Daniel Herbert-Cohen, Nadine Himelfarb, Calvin E. Hwang, Jacob D. Isserman, Joshua Jauregui, Joshua W. Joseph, Elena Kapilevich, Feras H. Khan, Sarvotham Kini, Karen A. Kinnaman, Ruth Lamm, Calvin Lee, Jarone Lee, Charles Lei, John Lemos, Daniel J. Lepp, Elisabeth Lessenich, Brandon Maughan, Julie Mayglothling, Kevin McConnell, Laura Medford-Davis, Kamal Medlej, Heather Meissen, Payal Modi, Joel Moll, Jolene H. Nakao, Matthew Nicholls, Lindsay Oelze, Carolyn Maher Overman, Viral Patel, Timothy C. Peck, Jeffrey Pepin, Candace Pettigrew, Byron Pitts, Zubaid Rafique, Chanu Rhee, Jonathan C. Roberts, Daniel Rolston, Steven C. Rougas, Benjamin Schnapp, Kathryn A. Seal, Raghu Seethala, Todd A. Seigel, Navdeep Sekhon, Kaushal Shah, Robert L. Sherwin, Kirill Shishlov, Ashley Shreves, Sebastian Siadecki, Jeffrey N. Siegelman, Liza Gonen Smith, Ted Stettner, Marie Carmelle Tabuteau, Joseph E. Tonna, N. Seth Trueger, Chad Van Ginkel, Bina Vasantharam, Graham Walker, Susan Wilcox, Sandra J. Williams, Matthew L. Wong, Nelson Wong, Samantha Wood, John Woodruff, Benjamin Zabar
- Edited by Kaushal Shah, Jarone Lee, Kamal Medlej, American University of Beirut, Scott D. Weingart
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- Practical Emergency Resuscitation and Critical Care
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- 05 November 2013
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- 24 October 2013, pp xi-xx
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Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis
- S. Tognin, A. Riecher-Rössler, E. M. Meisenzahl, S. J. Wood, C. Hutton, S. J. Borgwardt, N. Koutsouleris, A. R. Yung, P. Allen, L. J. Phillips, P. D. McGorry, I. Valli, D. Velakoulis, B. Nelson, J. Woolley, C. Pantelis, P. McGuire, A. Mechelli
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- Psychological Medicine / Volume 44 / Issue 3 / February 2014
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- 10 May 2013, pp. 489-498
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Background
Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.
MethodWe examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.
ResultsAt baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.
ConclusionsThese data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
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- By Ghazi Al-Rawas, Vazken Andréassian, Tianqi Ao, Stacey A. Archfield, Berit Arheimer, András Bárdossy, Trent Biggs, Günter Blöschl, Theresa Blume, Marco Borga, Helge Bormann, Gianluca Botter, Tom Brown, Donald H. Burn, Sean K. Carey, Attilio Castellarin, Francis Chiew, François Colin, Paulin Coulibaly, Armand Crabit, Barry Croke, Siegfried Demuth, Qingyun Duan, Giuliano Di Baldassarre, Thomas Dunne, Ying Fan, Xing Fang, Boris Gartsman, Alexander Gelfan, Mikhail Georgievski, Nick van de Giesen, David C. Goodrich, Hoshin V. Gupta, Khaled Haddad, David M. Hannah, H. A. P. Hapuarachchi, Hege Hisdal, Kamila Hlavčová, Markus Hrachowitz, Denis A. Hughes, Günter Humer, Ruud Hurkmans, Vito Iacobellis, Elena Ilyichyova, Hiroshi Ishidaira, Graham Jewitt, Shaofeng Jia, Jeffrey R. Kennedy, Anthony S. Kiem, Robert Kirnbauer, Thomas R. Kjeldsen, Jürgen Komma, Leonid M. Korytny, Charles N. Kroll, George Kuczera, Gregor Laaha, Henny A. J. van Lanen, Hjalmar Laudon, Jens Liebe, Shijun Lin, Göran Lindström, Suxia Liu, Jun Magome, Danny G. Marks, Dominic Mazvimavi, Jeffrey J. McDonnell, Brian L. McGlynn, Kevin J. McGuire, Neil McIntyre, Thomas A. McMahon, Ralf Merz, Robert A. Metcalfe, Alberto Montanari, David Morris, Roger Moussa, Lakshman Nandagiri, Thomas Nester, Taha B. M. J. Ouarda, Ludovic Oudin, Juraj Parajka, Charles S. Pearson, Murray C. Peel, Charles Perrin, John W. Pomeroy, David A. Post, Ataur Rahman, Liliang Ren, Magdalena Rogger, Dan Rosbjerg, José Luis Salinas, Jos Samuel, Eric Sauquet, Hubert H. G. Savenije, Takahiro Sayama, John C. Schaake, Kevin Shook, Murugesu Sivapalan, Jon Olav Skøien, Chris Soulsby, Christopher Spence, R. ‘Sri’ Srikanthan, Tammo S. Steenhuis, Jan Szolgay, Yasuto Tachikawa, Kuniyoshi Takeuchi, Lena M. Tallaksen, Dörthe Tetzlaff, Sally E. Thompson, Elena Toth, Peter A. Troch, Remko Uijlenhoet, Carl L. Unkrich, Alberto Viglione, Neil R. Viney, Richard M. Vogel, Thorsten Wagener, M. Todd Walter, Guoqiang Wang, Markus Weiler, Rolf Weingartner, Erwin Weinmann, Hessel Winsemius, Ross A. Woods, Dawen Yang, Chihiro Yoshimura, Andy Young, Gordon Young, Erwin Zehe, Yongqiang Zhang, Maichun C. Zhou
- Edited by Günter Blöschl, Technische Universität Wien, Austria, Murugesu Sivapalan, University of Illinois, Urbana-Champaign, Thorsten Wagener, University of Bristol, Alberto Viglione, Technische Universität Wien, Austria, Hubert Savenije, Technische Universiteit Delft, The Netherlands
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- Runoff Prediction in Ungauged Basins
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- 05 April 2013
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- 18 April 2013, pp ix-xiv
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8 - Prediction of low flows in ungauged basins
- Edited by Günter Blöschl, Technische Universität Wien, Austria, Murugesu Sivapalan, University of Illinois, Urbana-Champaign, Thorsten Wagener, University of Bristol, Alberto Viglione, Technische Universität Wien, Austria, Hubert Savenije, Technische Universiteit Delft, The Netherlands
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- Runoff Prediction in Ungauged Basins
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- 18 April 2013, pp 163-188
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Dietary patterns are associated with biomarkers of chronic low grade systemic inflammation in Scottish postmenopausal women: a prospective analysis
- A. D. Wood, W. G. Simpson, A. A. Gryka, A. C. Hardcastle, A. Mavroeidi, I. Rothnie, N. J. Vaughan, L. Aucott, G. G. Duthie, F. Thies, H. M. Macdonald
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- Proceedings of the Nutrition Society / Volume 71 / Issue OCE3 / 2012
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- 12 April 2013, E251
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- By Krista Adamek, Ana Luisa K. Albernaz, J. Marcio Ayres†, Andrew J. Baker, Karen L. Bales, Adrian A. Barnett, Christopher Barton, John M. Bates, Jennie Becker, Bruna M. Bezerra, Júlio César Bicca-Marques, Richard Bodmer, Jean P. Boubli, Mark Bowler, Sarah A. Boyle, Christini Barbosa Caselli, Janice Chism, Elena P. Cunningham, José Maria C. da Silva, Lesa C. Davies, Nayara de Alcântara Cardoso, Manuella A. de Souza, Stella de la Torre, Ana Gabriela de Luna, Thomas R. Defler, Anthony Di Fiore, Eduardo Fernandez-Duque, Stephen F. Ferrari, Wilsea M.B. Figueiredo-Ready, Tracy Frampton, Paul A. Garber, Brian W. Grafton, L. Tremaine Gregory, Maria L. Harada, Amy Harrison-Levine, Walter C. Hartwig, Stefanie Heiduck, Eckhard W. Heymann, André Hirsch, Leandro Jerusalinsky, Gareth Jones, Richard F. Kay, Martin M. Kowalewski, Shawn M. Lehman, Laura Marsh, Jesús Martinez, William A. Mason, Hope Matthews, Wynlyn McBride, Shona McCann-Wood, W. Scott McGraw, D. Jeffrey Meldrum, Sally P. Mendoza, Nohelia Mercado, Russell A. Mittermeier, Mirjam N. Nadjafzadeh, Marilyn A. Norconk, Robert Gary Norman, Marcela Oliveira, Marcelo M. Oliveira, Maria Juliana Ospina Rodríguez, Erwin Palacios, Suzanne Palminteri, Liliam P. Pinto, Marcio Port-Carvalho, Leila Porter, Carlos Portillo-Quintero, George Powell, Ghillean T. Prance, Rodrigo C. Printes, Pablo Puertas, P. Kirsten Pullen, Helder L. Queiroz, Luis Reginaldo R. Rodrigues, Adriana Rodríguez, Alfred L. Rosenberger, Anthony B. Rylands, Ricardo R. Santos, Horacio Schneider, Eleonore Z.F. Setz, Suleima S.B. Silva, José S. Silva Júnior, Andrew T. Smith, Marcelo C. Sousa, Antonio S. Souto, Wilson R. Spironello, Masanaru Takai, Marcelo F. Tejedor, Cynthia L. Thompson, Diego G. Tirira, Raul Tupayachi, Bernardo Urbani, Liza M. Veiga, Marianela Velilla, João Valsecchi, Jean-Christophe Vié, Tatiana M. Vieira, Suzanne E. Walker-Pacheco, Rob Wallace, Patricia C. Wright, Charles E. Zartman
- Edited by Liza M. Veiga, Universidade Federal do Pará, Brazil, Adrian A. Barnett, Roehampton University, London, Stephen F. Ferrari, Universidade Federal de Sergipe, Brazil, Marilyn A. Norconk, Kent State University, Ohio
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- Evolutionary Biology and Conservation of Titis, Sakis and Uacaris
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- 05 April 2013
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- 11 April 2013, pp xii-xv
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