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Systematic Review on the Mechanisms of Action of Psilocybin in the Treatment of Depression
- M. C. Q. Lin, H. Lee, V. W. L. Tsang, B. Chai, A. Howard, C. Uy, J. O. Elefante
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S416-S417
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Introduction
Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown.
ObjectivesAs the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aims to summarize the existing evidence of the mechanism of action with which psilocybin alleviates depressive symptoms, focusing specifically on the neurobiological effects of psilocybin in human subjects.
MethodsFour databases (Ovid MEDLINE, EMBASE, psychINFO, and Web of Science) were searched using a combination of MeSH terms and free text keywords in September 2021. The original search included both human and animal studies and must have included testing of the mechanism of action of psilocybin. Only antidepressant effects were considered, with no other mood disorders or psychiatric diagnoses included. Two independent researchers screened at every stage of the review, with a third researcher resolving any conflicts. Though a full systematic review outlining the current literature on the complete mechanisms of action of psilocybin on depression was conducted, this abstract will focus specifically on the nine papers that included human subjects, disregarding the five animal models. PROSPERO registration number: 282710.
ResultsAfter removing duplicates, the search identified 2193 papers and forty-nine were selected for full text review. Out of nine papers outlining the mechanisms of action of psilocybin use in human subjects, three papers investigated psilocybin’s effect on serotonin or glutamate receptor activity, two found an increase in synaptogenesis in regions such as the medial frontal cortex and hippocampus. Four found variation in blood flow to the amygdala, two found altered blood flow to the prefrontal cortex, and one found a reduction in delta power during sleep. Four papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex.
ConclusionsOverall, the exact mechanism of psilocybin’s potential antidepressant effect remains unclear. Multiple pathways may be involved, including alterations in serotonin and glutamate receptor activity, as well as shifts in amygdala activity, neurogenesis, and functional connectivity in various brain regions. The relative lack of studies, and the variety of neurobiological modalities and endpoints used challenged the consolidation of data into consensus findings. Further studies are needed to better characterize psilocybin’s mechanism of action and to better understand the clinical effects of the use of psilocybin in the treatment of depression.
Disclosure of InterestNone Declared
WALLABY Pilot Survey: Public release of HI kinematic models for more than 100 galaxies from phase 1 of ASKAP pilot observations
- N. Deg, K. Spekkens, T. Westmeier, T. N. Reynolds, P. Venkataraman, S. Goliath, A. X. Shen, R. Halloran, A. Bosma, B Catinella, W. J. G. de Blok, H. Dénes, E. M. DiTeodoro, A. Elagali, B.-Q. For, C Howlett, G. I. G. Józsa, P. Kamphuis, D. Kleiner, B Koribalski, K. Lee-Waddell, F. Lelli, X. Lin, C. Murugeshan, S. Oh, J. Rhee, T. C. Scott, L. Staveley-Smith, J. M. van der Hulst, L. Verdes-Montenegro, J. Wang, O. I. Wong
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 39 / 2022
- Published online by Cambridge University Press:
- 15 November 2022, e059
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We present the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) Pilot Phase I Hi kinematic models. This first data release consists of Hi observations of three fields in the direction of the Hydra and Norma clusters, and the NGC 4636 galaxy group. In this paper, we describe how we generate and publicly release flat-disk tilted-ring kinematic models for 109/592 unique Hi detections in these fields. The modelling method adopted here—which we call the WALLABY Kinematic Analysis Proto-Pipeline (WKAPP) and for which the corresponding scripts are also publicly available—consists of combining results from the homogeneous application of the FAT and 3DBarolo algorithms to the subset of 209 detections with sufficient resolution and $S/N$ in order to generate optimised model parameters and uncertainties. The 109 models presented here tend to be gas rich detections resolved by at least 3–4 synthesised beams across their major axes, but there is no obvious environmental bias in the modelling. The data release described here is the first step towards the derivation of similar products for thousands of spatially resolved WALLABY detections via a dedicated kinematic pipeline. Such a large publicly available and homogeneously analysed dataset will be a powerful legacy product that that will enable a wide range of scientific studies.
WALLABY pilot survey: Public release of H i data for almost 600 galaxies from phase 1 of ASKAP pilot observations
- T. Westmeier, N. Deg, K. Spekkens, T. N. Reynolds, A. X. Shen, S. Gaudet, S. Goliath, M. T. Huynh, P. Venkataraman, X. Lin, T. O’Beirne, B. Catinella, L. Cortese, H. Dénes, A. Elagali, B.-Q. For, G. I. G. Józsa, C. Howlett, J. M. van der Hulst, R. J. Jurek, P. Kamphuis, V. A. Kilborn, D. Kleiner, B. S. Koribalski, K. Lee-Waddell, C. Murugeshan, J. Rhee, P. Serra, L. Shao, L. Staveley-Smith, J. Wang, O. I. Wong, M. A. Zwaan, J. R. Allison, C. S. Anderson, Lewis Ball, D. C.-J. Bock, D. Brodrick, J. D. Bunton, F. R. Cooray, N. Gupta, D. B. Hayman, E. K. Mahony, V. A. Moss, A. Ng, S. E. Pearce, W. Raja, D. N. Roxby, M. A. Voronkov, K. A. Warhurst, H. M. Courtois, K. Said
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 39 / 2022
- Published online by Cambridge University Press:
- 15 November 2022, e058
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We present WALLABY pilot data release 1, the first public release of H i pilot survey data from the Wide-field ASKAP L-band Legacy All-sky Blind Survey (WALLABY) on the Australian Square Kilometre Array Pathfinder. Phase 1 of the WALLABY pilot survey targeted three $60\,\mathrm{deg}^{2}$ regions on the sky in the direction of the Hydra and Norma galaxy clusters and the NGC 4636 galaxy group, covering the redshift range of $z \lesssim 0.08$ . The source catalogue, images and spectra of nearly 600 extragalactic H i detections and kinematic models for 109 spatially resolved galaxies are available. As the pilot survey targeted regions containing nearby group and cluster environments, the median redshift of the sample of $z \approx 0.014$ is relatively low compared to the full WALLABY survey. The median galaxy H i mass is $2.3 \times 10^{9}\,{\rm M}_{{\odot}}$ . The target noise level of $1.6\,\mathrm{mJy}$ per 30′′ beam and $18.5\,\mathrm{kHz}$ channel translates into a $5 \sigma$ H i mass sensitivity for point sources of about $5.2 \times 10^{8} \, (D_{\rm L} / \mathrm{100\,Mpc})^{2} \, {\rm M}_{{\odot}}$ across 50 spectral channels ( ${\approx} 200\,\mathrm{km \, s}^{-1}$ ) and a $5 \sigma$ H i column density sensitivity of about $8.6 \times 10^{19} \, (1 + z)^{4}\,\mathrm{cm}^{-2}$ across 5 channels ( ${\approx} 20\,\mathrm{km \, s}^{-1}$ ) for emission filling the 30′′ beam. As expected for a pilot survey, several technical issues and artefacts are still affecting the data quality. Most notably, there are systematic flux errors of up to several 10% caused by uncertainties about the exact size and shape of each of the primary beams as well as the presence of sidelobes due to the finite deconvolution threshold. In addition, artefacts such as residual continuum emission and bandpass ripples have affected some of the data. The pilot survey has been highly successful in uncovering such technical problems, most of which are expected to be addressed and rectified before the start of the full WALLABY survey.
What makes the psychosis ‘clinical high risk’ state risky: psychosis itself or the co-presence of a non-psychotic disorder?
- Laila Hasmi, Lotta-Katrin Pries, Margreet ten Have, Ron de Graaf, Saskia van Dorsselaer, Maarten Bak, Gunter Kenis, Alexander Richards, Bochao D. Lin, Michael C. O'Donovan, Jurjen J. Luykx, Bart P.F. Rutten, Sinan Guloksuz, Jim van Os
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 30 / 2021
- Published online by Cambridge University Press:
- 06 July 2021, e53
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Aims
Although attenuated psychotic symptoms in the psychosis clinical high-risk state (CHR-P) almost always occur in the context of a non-psychotic disorder (NPD), NPD is considered an undesired ‘comorbidity’ epiphenomenon rather than an integral part of CHR-P itself. Prospective work, however, indicates that much more of the clinical psychosis incidence is attributable to prior mood and drug use disorders than to psychosis clinical high-risk states per se. In order to examine this conundrum, we analysed to what degree the ‘risk’ in CHR-P is indexed by co-present NPD rather than attenuated psychosis per se.
MethodsWe examined the incidence of early psychotic experiences (PE) with and without NPD (mood disorders, anxiety disorders, alcohol/drug use disorders), in a prospective general population cohort (n = 6123 at risk of incident PE at baseline). Four interview waves were conducted between 2007 and 2018 (NEMESIS-2). The incidence of PE, alone (PE-only) or with NPD (PE + NPD) was calculated, as were differential associations with schizophrenia polygenic risk score (PRS-Sz), environmental, demographical, clinical and cognitive factors.
ResultsThe incidence of PE + NPD (0.37%) was lower than the incidence of PE-only (1.04%), representing around a third of the total yearly incidence of PE. Incident PE + NPD was, in comparison with PE-only, differentially characterised by poor functioning, environmental risks, PRS-Sz, positive family history, prescription of antipsychotic medication and (mental) health service use.
ConclusionsThe risk in ‘clinical high risk’ states is mediated not by attenuated psychosis per se but specifically the combination of attenuated psychosis and NPD. CHR-P/APS research should be reconceptualised from a focus on attenuated psychotic symptoms with exclusion of non-psychotic DSM-disorders, as the ‘pure' representation of a supposedly homotypic psychosis risk state, towards a focus on poor-outcome NPDs, characterised by a degree of psychosis admixture, on the pathway to psychotic disorder outcomes.
Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study
- Gamze Erzin, Lotta-Katrin Pries, Jim van Os, Laura Fusar-Poli, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric-Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, Celso Arango, Micheal C. O’Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 19 March 2021, e25
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Background
A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
MethodsThis cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
ResultsES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
ConclusionsOur findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
- L.-K. Pries, G. A. Dal Ferro, J. van Os, P. Delespaul, G. Kenis, B. D. Lin, J. J. Luykx, A. L. Richards, B. Akdede, T. Binbay, V. Altınyazar, B. Yalınçetin, G. Gümüş-Akay, B. Cihan, H. Soygür, H. Ulaş, E. Şahin Cankurtaran, S. Ulusoy Kaymak, M. M. Mihaljevic, S. Andric Petrovic, T. Mirjanic, M. Bernardo, G. Mezquida, S. Amoretti, J. Bobes, P. A. Saiz, M. Paz García-Portilla, J. Sanjuan, E. J. Aguilar, J. L. Santos, E. Jiménez-López, M. Arrojo, A. Carracedo, G. López, J. González-Peñas, M. Parellada, N. P. Maric, C. Atbaşoğlu, A. Ucok, K. Alptekin, M. Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, C. Arango, M. O'Donovan, S. Tosato, B. P. F. Rutten, S. Guloksuz
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 17 November 2020, e182
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Aims
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
MethodsThe sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
ResultsBoth genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
ConclusionsThe interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
A replication study of JTC bias, genetic liability for psychosis and delusional ideation
- Cécile Henquet, Jim van Os, Lotta K. Pries, Christian Rauschenberg, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem S. Cankurtaran, Semra U. Kaymak, Marina M. Mihaljevic, Sanja S. Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria P. García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose L. Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram C. Saka, Celso Arango, Michael O'Donovan, Bart P.F. Rutten, Sinan Gülöksüz
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- Journal:
- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 13 October 2020, pp. 1777-1783
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Background
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
MethodsData were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
ResultsJTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
ConclusionsThese findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
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.
Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains
- R. Blakey, S. Ranlund, E. Zartaloudi, W. Cahn, S. Calafato, M. Colizzi, B. Crespo-Facorro, C. Daniel, Á. Díez-Revuelta, M. Di Forti, GROUP, C. Iyegbe, A. Jablensky, R. Jones, M.-H. Hall, R. Kahn, L. Kalaydjieva, E. Kravariti, K. Lin, C. McDonald, A. M. McIntosh, PEIC, M. Picchioni, J. Powell, A. Presman, D. Rujescu, K. Schulze, M. Shaikh, J. H. Thygesen, T. Toulopoulou, N. Van Haren, J. Van Os, M. Walshe, WTCCC2, R. M. Murray, E. Bramon
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- Journal:
- Psychological Medicine / Volume 48 / Issue 8 / June 2018
- Published online by Cambridge University Press:
- 02 November 2017, pp. 1325-1340
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Background
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
MethodsThis multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
ResultsThe P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
ConclusionsThe P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Heritability and GWAS Studies for Monocyte–Lymphocyte Ratio
- Bochao D. Lin, Gonneke Willemsen, Iryna O. Fedko, Rick Jansen, Brenda Penninx, E. de Geus, C. Kluft, JoukeJan Hottenga, Dorret I. Boomsma
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- Journal:
- Twin Research and Human Genetics / Volume 20 / Issue 2 / April 2017
- Published online by Cambridge University Press:
- 14 February 2017, pp. 97-107
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The monocyte–lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-family population. Data were obtained in 9,501 individuals from the Netherlands Twin Register. We used regression analyses to determine the effects of age, sex, smoking, and body mass index (BMI) on MLR and its subcomponents. Data on twins, siblings and parents (N = 7,513) were analyzed by genetic structural equation modeling to establish heritability and genome wide single nucleotide polymorphism (SNP) data from a genotyped subsample (N = 5,892) and used to estimate heritability explained by SNPs. SNP and phenotype data were also analyzed in a genome-wide association study to identify the genes involved in MLR. Linkage disequilibrium (LD) score regression and expression quantitative trait loci (eQTL) analyses were performed to further explore the genetic findings. Results showed that age, sex, and age × sex interaction effects were present for MLR and its subcomponents. Variation in MLR was not related to BMI, but smoking was positively associated with MLR. Heritability was estimated at 40% for MLR, 58% for monocyte, and 58% for lymphocyte count. The Genome-wide association study (GWAS) identified a locus on ITGA4 that was associated with MLR and only marginally significantly associated with monocyte count. For monocyte count, additional genetic variants were identified on ITPR3, LPAP1, and IRF8. For lymphocyte count, GWAS provided no significant findings. Taking all measured SNPs together, their effects accounted for 13% of the heritability of MLR, while all known and identified genetic loci explained 1.3% of variation in MLR. eQTL analyses showed that these genetic variants were unlikely to be eQTLs. In conclusion, variation in MLR level in the general population is heritable and influenced by age, sex, and smoking. We identified gene variants in the ITGA4 gene associated with variation in MLR. The significant SNP-heritability indicates that more genetic variants are likely to be involved.
Contributors
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- By Eric L. Anderson, Dennis Barton, Annette L. Beautrais, O. Joseph Bienvenu, Ashley D. Bone, Curtis Bone, Sharon Bord, Emily Bost-Baxter, Arjun Chanmugam, Michael Clark, J. Raymond DePaulo, Emily Frosch, Angela S. Guarda, James Harrison, Frederick Houts, Lisa S. Hovermale, Geetha Jayaram, Patrick Kelly, Gregory Luke Larkin, Valerie R. Lint, Cynthia Major-Lewis, Catherine A. Marco, Darren Mareiniss, Dave Milzman, Melinda J. Ortmann, Theodosia Paclawskyj, Graham W. Redgrave, Paul P. Rega, Mustapha Saheed, Eric Samstad, Karen Swartz, Dyanne Simpson, Hahn Soe-Lin, Roshni I. Thakore, Glenn Treisman, Patrick Triplett, Crystal Watkins, Holly C. Wilcox
- Edited by Arjun Chanmugam, Patrick Triplett, Gabor Kelen
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- Emergency Psychiatry
- Published online:
- 05 May 2013
- Print publication:
- 09 May 2013, pp viii-x
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The Current Trends in SBS and phase conjugation
- T. Omatsu, H.J. Kong, S. Park, S. Cha, H. Yoshida, K. Tsubakimoto, H. Fujita, N. Miyanaga, M. Nakatsuka, Y. Wang, Z. Lu, Z. Zheng, Y. Zhang, M. Kalal, O. Slezak, M. Ashihara, T. Yoshino, K. Hayashi, Y. Tokizane, M. Okida, K. Miyamoto, K. Toyoda, A.A. Grabar, Md. M. Kabir, Y. Oishi, H. Suzuki, F. Kannari, C. Schaefer, K.R. Pandiri, M. Katsuragawa, Y.L. Wang, Z.W. Lu, S.Y. Wang, Z.X. Zheng, W.M. He, D.Y. Lin, W.L.J. Hasi, X.Y. Guo, H.H. Lu, M.L. Fu, S. Gong, X.Z. Geng, R.P. Sharma, P. Sharma, S. Rajput, A.K. Bhardwaj, C.Y. Zhu, W. Gao
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- Journal:
- Laser and Particle Beams / Volume 30 / Issue 1 / March 2012
- Published online by Cambridge University Press:
- 30 March 2012, pp. 117-174
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The current trends in stimulated Brillouin scattering and optical phase conjugation are overviewed. This report is formed by the selected papers presented in the “Fifth International Workshop on stimulated Brillouin scattering and phase conjugation 2010” in Japan. The nonlinear properties of phase conjugation based on stimulated Brillouin scattering and photo-refraction can compensate phase distortions in the high power laser systems, and they will also open up potentially novel laser technologies, e.g., phase stabilization, beam combination, pulse compression, ultrafast pulse shaping, and arbitrary waveform generation.
Prominence seismology using ground- and space-based observations
- M. Faurobert, C. Fang, T. Corbard, J.L. Ballester, I. Arregui, R. Oliver, J. Terradas, R. Soler, Y. Lin, O. Engvold, O. Langagen, L.H.M. Rouppe van der Voort
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- Journal:
- European Astronomical Society Publications Series / Volume 55 / 2012
- Published online by Cambridge University Press:
- 27 June 2012, pp. 169-174
- Print publication:
- 2012
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Ground- and space-based observations have confirmed the presence of oscillatory motions in prominences and they have been interpreted in terms of magnetohydrodynamic (MHD) waves. This interpretation opens the door to perform prominence seismology, whose main aim is to determine physical parameters in magnetic and plasma structures (prominences) that are difficult to measure by direct means. Here, two prominence seismology applications are presented.
Contributors
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Book:
- Essential Clinical Anesthesia
- Published online:
- 05 January 2012
- Print publication:
- 11 July 2011, pp xv-xxviii
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Contributors
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- By Adil O. S. Bahathiq, Ying C. Cheong, Ovrang Djahanbakhch, Adrian R. Eley, Mohammad Ezzati, Nadia Kabli, Stephen R. Killick, Hany Lashen, William L. Ledger, Kai-Fai Lee, Yin-Lau Lee, Tin-Chiu Li, McIlveen, B. Myvanwy, Chun Y. Ng, Bassem Refaat, Ertan Saridogan, Seang Lin Tan, Geoffrey H. Trew, Togas Tulandi, William S. B. Yeung
- Edited by William L. Ledger, University of Sheffield, Seang Lin Tan, McGill University, Montréal, Adil O. S. Bahathiq
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- Book:
- The Fallopian Tube in Infertility and IVF Practice
- Published online:
- 06 July 2010
- Print publication:
- 29 March 2010, pp vii-viii
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- By Harold P. Adams, Colum F. Amory, Anne Angelillo-Scherrer, Irena Anselm, Marcel Arnold, Robert W. Baloh, Ralf W. Baumgartner, José Biller, Valérie Biousse, Matthias Bischof, Julien Bogousslavsky, Natan M. Bornstein, Marie Germaine Bousser, Robin L. Brey, John C. M. Brust, Alan Bryer, Olivier Calvetti, Louis R. Caplan, José Castillo, Hugues Chabriat, Chin-Sang Chung, Charlotte Cordonnier, Steven C. Cramer, Luís Cunha, Rima M. Dafer, John F. Dashe, Cyrus K. Dastur, Antonio Dávalos, Larry E. Davis, Patricia Davis, Stephen M. Davis, Jan L. De Bleecker, Michael A. De Georgia, Amir R. Dehdashti, Oscar H. Del Brutto, Jacques L. De Reuck, Hans-Christoph Diener, Kathleen B. Digre, Vivian U. Fritz, Nancy Futrell, Bhuwan P. Garg, Philip B. Gorelick, Glenn D. Graham, Alexander Y. Gur, John J. Halperin, Michael Hennerici, Isabel Lestro Henriques, Roberto C. Heros, Daniel B. Hier, Lorenz Hirt, Joanna C. Jen, Taro Kaibara, Sumit Kapoor, Sarosh M. Katrak, Siddharth Kharkar, Walter J. Koroshetz, Monisha Kumar, Sandeep Kumar, Emre Kumral, Tobias Kurth, Rogelio Leira, Steven R. Levine, Didier Leys, Doris Lin, Jonathan Lipton, Alfredo M. Lopez-Yunez, Betsy B. Love, Ayrton Roberto Massaro, Heinrich P. Mattle, Manu Mehdiratta, John H. Menkes, Philippe Metellus, Reto Meuli, Patrik Michel, Panayiotis Mitsias, Jorge Moncayo-Gaete, Julien Morier, Krassen Nedeltchev, Bernhard Neundörfer, Olukemi A. Olugemo, Nikolaos I. H. Papamitsakis, Stephen D. Reck, Luca Regli, Marc D. Reichhart, Daniele Rigamonti, Michael J. Rivkin, E. Steve Roach, Jose F. Roldan, David Z. Rose, Daniel M. Rosenbaum, N. Paul Rosman, Elayna O. Rubens, Sean I. Savitz, Marc Schapira, Robert J. Schwartzman, Magdy Selim, Yukito Shinohara, Aneesh B. Singhal, Michael A. Sloan, Barney J. Stern, Mathias Sturzenegger, Oriana Thompson, A. Wesley Thevathasan, Jonathan D. Trobe, Michael Varner, Dana Védy, Jorge Vidaurre, Engin Y. Yilmaz, Khaled Zamel, Mathieu Zuber
- Edited by Louis R. Caplan, Julien Bogousslavsky
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- Book:
- Uncommon Causes of Stroke
- Published online:
- 06 January 2010
- Print publication:
- 09 October 2008, pp ix-xiv
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Trends in stimulated Brillouin scattering and optical phase conjugation
- M. Ostermeyer, H.J. Kong, V.I. Kovalev, R.G. Harrison, A.A. Fotiadi, P. Mégret, M. Kalal, O. Slezak, J.W. Yoon, J.S. Shin, D.H. Beak, S.K. Lee, Z. Lü, S. Wang, D. Lin, J.C. Knight, N.E. Kotova, A. Sträßer, A. Scheikh-Obeid, T. Riesbeck, S. Meister, H.J. Eichler, Y. Wang, W. He, H. Yoshida, H. Fujita, M. Nakatsuka, T. Hatae, H. Park, C. Lim, T. Omatsu, K. Nawata, N. Shiba, O.L. Antipov, M.S. Kuznetsov, N.G. Zakharov
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- Journal:
- Laser and Particle Beams / Volume 26 / Issue 3 / September 2008
- Published online by Cambridge University Press:
- 09 June 2008, pp. 297-362
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An overview on current trends in stimulated Brillouin scattering and optical phase conjugation is given. This report is based on the results of the “Second International Workshop on stimulated Brillouin scattering and phase conjugation” held in Potsdam/Germany in September 2007. The properties of stimulated Brillouin scattering are presented for the compensation of phase distortions in combination with novel laser technology like ceramics materials but also for e.g., phase stabilization, beam combination, and slow light. Photorefractive nonlinear mirrors and resonant refractive index gratings are addressed as phase conjugating mirrors in addition.
Mental disorders among persons with arthritis: results from the World Mental Health Surveys
- Y. He, M. Zhang, E. H. B. Lin, R. Bruffaerts, J. Posada-Villa, M. C. Angermeyer, D. Levinson, G. de Girolamo, H. Uda, Z. Mneimneh, C. Benjet, R. de Graaf, K. M. Scott, O. Gureje, S. Seedat, J. M. Haro, E. J. Bromet, J. Alonso, V. Kovess, M. von Korff, R. Kessler
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- Journal:
- Psychological Medicine / Volume 38 / Issue 11 / November 2008
- Published online by Cambridge University Press:
- 26 February 2008, pp. 1639-1650
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Background
Prior studies in the USA have reported higher rates of mental disorders among persons with arthritis but no cross-national studies have been conducted. In this study the prevalence of specific mental disorders among persons with arthritis was estimated and their association with arthritis across diverse countries assessed.
MethodThe study was a series of cross-sectional population sample surveys. Eighteen population surveys of household-residing adults were carried out in 17 countries in different regions of the world. Most were carried out between 2001 and 2002, but others were completed as late as 2007. Mental disorders were assessed with the World Health Organization (WHO) World Mental Health–Composite International Diagnostic Interview (WMH-CIDI). Arthritis was ascertained by self-report. The association of anxiety disorders, mood disorders and alcohol use disorders with arthritis was assessed, controlling for age and sex. Prevalence rates for specific mental disorders among persons with and without arthritis were calculated and odds ratios (ORs) with 95% confidence intervals were used to estimate the association.
ResultsAfter adjusting for age and sex, specific mood and anxiety disorders occurred among persons with arthritis at higher rates than among persons without arthritis. Alcohol abuse/dependence showed a weaker and less consistent association with arthritis. The pooled estimates of the age- and sex-adjusted ORs were about 1.9 for mood disorders and for anxiety disorders and about 1.5 for alcohol abuse/dependence among persons with versus without arthritis. The pattern of association between specific mood and anxiety disorders and arthritis was similar across countries.
ConclusionsMood and anxiety disorders occur with greater frequency among persons with arthritis than those without arthritis across diverse countries. The strength of association of specific mood and anxiety disorders with arthritis was generally consistent across disorders and across countries.
The case for strategic international alliances to harness nutritional genomics for public and personal health†
- Jim Kaput, Jose M. Ordovas, Lynnette Ferguson, Ben van Ommen, Raymond L. Rodriguez, Lindsay Allen, Bruce N. Ames, Kevin Dawson, Bruce German, Ronald Krauss, Wasyl Malyj, Michael C. Archer, Stephen Barnes, Amelia Bartholomew, Ruth Birk, Peter van Bladeren, Kent J. Bradford, Kenneth H. Brown, Rosane Caetano, David Castle, Ruth Chadwick, Stephen Clarke, Karine Clément, Craig A. Cooney, Dolores Corella, Ivana Beatrice Manica da Cruz, Hannelore Daniel, Troy Duster, Sven O. E. Ebbesson, Ruan Elliott, Susan Fairweather-Tait, Jim Felton, Michael Fenech, John W. Finley, Nancy Fogg-Johnson, Rosalynn Gill-Garrison, Michael J. Gibney, Peter J. Gillies, Jan-Ake Gustafsson, John L. Hartman IV, Lin He, Jae-Kwan Hwang, Jean-Philippe Jais, Yangsoo Jang, Hans Joost, Claudine Junien, Mitchell Kanter, Warren A. Kibbe, Berthold Koletzko, Bruce R. Korf, Kenneth Kornman, David W. Krempin, Dominique Langin, Denis R. Lauren, Jong Ho Lee, Gilbert A. Leveille, Su-Ju Lin, John Mathers, Michael Mayne, Warren McNabb, John A. Milner, Peter Morgan, Michael Muller, Yuri Nikolsky, Frans van der Ouderaa, Taesun Park, Norma Pensel, Francisco Perez-Jimenez, Kaisa Poutanen, Matthew Roberts, Wim H.M. Saris, Gertrud Schuster, Andrew N. Shelling, Artemis P. Simopoulos, Sue Southon, E. Shyong Tai, Bradford Towne, Paul Trayhurn, Ricardo Uauy, Willard J. Visek, Craig Warden, Rick Weiss, John Wiencke, Jack Winkler, George L. Wolff, Xi Zhao-Wilson, Jean-Daniel Zucker
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- Journal:
- British Journal of Nutrition / Volume 94 / Issue 5 / November 2005
- Published online by Cambridge University Press:
- 08 March 2007, pp. 623-632
- Print publication:
- November 2005
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Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
The Influence of Defects on Compatibility and Yield of the HfO2-PolySilicon Gate Stack for CMOS Integration
- V. S. Kaushik, S. DeGendt, R. Carter, M. Claes, E. Rohr, L. Pantisano, J. Kluth, A. Kerber, V. Cosnier, E. Cartier, W. Tsai, E. Young, M. Green, J. Chen, S-A. Jang, S. Lin, A. Delabie, S. V. Elshocht, Y. Manabe, O. Richard, C. Zhao, H. Bender, M. Caymax, M. Heyns
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- Journal:
- MRS Online Proceedings Library Archive / Volume 747 / 2002
- Published online by Cambridge University Press:
- 11 February 2011, T6.7/N8.7
- Print publication:
- 2002
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Hafnium-based dielectrics are under wide consideration for high-K gate dielectric applications. Since the gate electrode typically used in CMOS integration consists of polysilicon with n- or p-type dopants, compatibility of the HfO2 layer with the polySi deposition and dopant activation steps is critical. Capacitors were fabricated with HfO2 films deposited by ALD and MOCVD, and using polysilicon gate electrodes deposited by CVD processes. These devices showed leakage failures with yields that were observed to depend on the area, dielectric thickness and annealing conditions during the process. Investigation of the root cause of these leakage failures suggested that the leakage failures may be caused by a defect-related mechanism. The implication of this is that the leakage occurs at localized ‘defect’ sites rather than broadly through the HfO2 layer. Emission microscopy analysis and physical characterization of the HfO2 film were used to corroborate the proposed model. Defect density was observed to be strongly dependent on the processing of the dielectric film. In order to make Hf-based dielectric stacks compatible with polysilicon for conventional CMOS transistor integration with acceptable yield, further postdeposition treatment may be necessary to eliminate or cure the defects.