304 results
The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis
- Kuan-Yu Pan, Lonneke van Tuijl, Maartje Basten, Judith J. M. Rijnhart, Alexander de Graeff, Joost Dekker, Mirjam I. Geerlings, Adriaan Hoogendoorn, Adelita V. Ranchor, Roel Vermeulen, Lützen Portengen, Adri C. Voogd, Jessica Abell, Philip Awadalla, Aartjan T. F. Beekman, Ottar Bjerkeset, Andy Boyd, Yunsong Cui, Philipp Frank, Henrike Galenkamp, Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A. L. Kok, Steinar Krokstad, Flora E. van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W. J. H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G. M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. van der Willik, Femke Lamers
-
- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 29 April 2024, pp. 1-14
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
MethodsTwo-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
ResultsSmoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
ConclusionsSmoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
Nomenclature of the Micas
- Milan Rieder, Giancarlo Cavazzini, Yurii S. D'yakonov, Viktor A. Frank-Kamenetskii, Glauco Gottardi, Stephen Guggenheim, Pavel W. Koval’, Georg Müller, Ana M. R. Neiva, Edward W. Radoslovich, Jean-Louis Robert, Francesco P. Sassi, Hiroshi Takeda, Zdeněk Weiss, David R. Wones
-
- Journal:
- Clays and Clay Minerals / Volume 46 / Issue 5 / October 1998
- Published online by Cambridge University Press:
- 28 February 2024, pp. 586-595
-
- Article
- Export citation
-
End members and species defined with permissible ranges of composition are presented for the true micas, the brittle micas and the interlayer-cation-deficient micas. The determination of the crystallochemical formula for different available chemical data is outlined, and a system of modifiers and suffixes is given to allow the expression of unusual chemical substitutions or polytypic stacking arrangements. Tables of mica synonyms, varieties, ill-defined materials and a list of names formerly or erroneously used for micas are presented. The Mica Subcommittee was appointed by the Commission on New Minerals and Mineral Names (“Commission”) of the International Mineralogical Association (IMA). The definitions and recommendations presented were approved by the Commission.
Scoping article: research frontiers on the governance of the Sustainable Development Goals
- Part of
- Thomas Hickmann, Frank Biermann, Carole-Anne Sénit, Yixian Sun, Magdalena Bexell, Mitzi Bolton, Basil Bornemann, Jecel Censoro, Aurelie Charles, Dominique Coy, Frederik Dahlmann, Mark Elder, Felicitas Fritzsche, Thiago Gehre Galvão, Jarrod Grainger-Brown, Cristina Inoue, Kristina Jönsson, Montserrat Koloffon Rosas, Kerstin Krellenberg, Enayat Moallemi, Ivonne Lobos Alva, Shirin Malekpour, Dianty Ningrum, Aneliya Paneva, Lena Partzsch, Rodrigo Ramiro, Rob Raven, Eszter Szedlacsek, John Thompson, Melanie van Driel, Jéssica Viani Damasceno, Robert Webb, Sabine Weiland
-
- Journal:
- Global Sustainability / Volume 7 / 2024
- Published online by Cambridge University Press:
- 24 January 2024, e7
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Non-Technical Summary
This article takes stock of the 2030 Agenda and focuses on five governance areas. In a nutshell, we see a quite patchy and often primarily symbolic uptake of the global goals. Although some studies highlight individual success stories of actors and institutions to implement the goals, it remains unclear how such cases can be upscaled and develop a broader political impact to accelerate the global endeavor to achieve sustainable development. We hence raise concerns about the overall effectiveness of governance by goal-setting and raise the question of how we can make this mode of governance more effective.
Technical SummaryA recent meta-analysis on the political impact of the Sustainable Development Goals (SDGs) has shown that these global goals are moving political processes forward only incrementally, with much variation across countries, sectors, and governance levels. Consequently, the realization of the 2030 Agenda for Sustainable Development remains uncertain. Against this backdrop, this article explores where and how incremental political changes are taking place due to the SDGs, and under what conditions these developments can bolster sustainability transformations up to 2030 and beyond. Our scoping review builds upon an online expert survey directed at the scholarly community of the ‘Earth System Governance Project’ and structured dialogues within the ‘Taskforce on the SDGs’ under this project. We identified five governance areas where some effects of the SDGs have been observable: (1) global governance, (2) national policy integration, (3) subnational initiatives, (4) private governance, and (5) education and learning for sustainable development. This article delves deeper into these governance areas and draws lessons to guide empirical research on the promises and pitfalls of accelerating SDG implementation.
Social Media SummaryAs SDG implementation lags behind, this article explores 5 governance areas asking how to strengthen the global goals.
4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery
- Bistra Zheleva, Amy Verstappen, David M. Overman, Farhan Ahmad, Sulafa K.M. Ali, Zohair Y. Al Halees, Joumana Ghandour Atallah, Isabella E. Badhwar, Carissa Baker-Smith, Maria Balestrini, Amy Basken, Jonah S. Bassuk, Lee Benson, Horacio Capelli, Santo Carollo, Devyani Chowdhury, M. Sertaç Çiçek, Mitchell I. Cohen, David S. Cooper, John E. Deanfield, Joseph Dearani, Blanca del Valle, Kathryn M. Dodds, Junbao Du, Frank Edwin, Ekanem Ekure, Nurun Nahar Fatema, Anu Gomanju, Babar Hasan, Lewis Henry, Christopher Hugo-Hamman, Krishna S. Iyer, Marcelo B. Jatene, Kathy J. Jenkins, Tara Karamlou, Tom R. Karl, James K. Kirklin, Christián Kreutzer, Raman Krishna Kumar, Keila N. Lopez, Alexis Palacios Macedo, Bradley S. Marino, Eva M. Marwali, Folkert J. Meijboom, Sandra S. Mattos, Hani Najm, Dan Newlin, William M. Novick, Sir Shakeel A. Qureshi, Budi Rahmat, Robert Raylman, Irfan Levent Saltik, Craig Sable, Nestor Sandoval, Anita Saxena, Emma Scanlan, Gary F. Sholler, Jodi Smith, James D. St Louis, Christo I. Tchervenkov, Koh Ghee Tiong, Vladimiro Vida, Susan Vosloo, Douglas J. “DJ” Weinstein, James L. Wilkinson, Liesl Zuhlke, Jeffrey P. Jacobs
-
- Journal:
- Cardiology in the Young / Volume 33 / Issue 8 / August 2023
- Published online by Cambridge University Press:
- 24 August 2023, pp. 1277-1287
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
The effects of advanced factor analysis approaches on outcomes in randomised trials for depression: protocol for secondary analysis of individual participant data
- Frank Doyle, David Byrne, Robert M. Carney, Pim Cuijpers, Alexandra L. Dima, Kenneth Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Shane Kelly, Stephen McBride, Emma Wallace, Fiona Boland
-
- Journal:
- BJPsych Open / Volume 9 / Issue 5 / September 2023
- Published online by Cambridge University Press:
- 11 August 2023, e157
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, and may increase treatment effect sizes in depression treatment trials.
AimsWe aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.
MethodWe will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) as the outcome measure. Exploratory and confirmatory factor analytic approaches will be used to determine pre-treatment (baseline) and post-treatment models of depression, in terms of the number of factors and weighted scores of each item. Differences in the derived factor scores between baseline and outcome measurements will yield an effect size for factor-informed depression change. The difference between the factor-informed effect size and each original trial effect size, calculated with total HRSD-17 scores, will be determined, and the differences modelled with meta-analytic approaches. Risk differences for proportions of patients who achieved remission will also be evaluated. Furthermore, measurement invariance methods will be used to assess potential gender differences.
ConclusionsOur approach will determine whether adopting advanced psychometric analyses can improve precision and better estimate effect sizes in antidepressant treatment trials. The proposed methods could have implications for future trials and other types of studies that use patient-reported outcome measures.
Sexual health experiences of women and non-binary people with early psychosis: qualitative study
- Lucy C. Barker, Simone N. Vigod, Zakia Hussain, Julia France, Ananka Rodriguez, Shakked Lubotzky-Gete, Suze Berkhout, Robert Dmytryshyn, Sheila Dunn, Renu Gupta, Fardous Hosseiny, Frank Sirotich, Sophie Soklaridis, Aristotle Voineskos, Juveria Zaheer
-
- Journal:
- BJPsych Open / Volume 9 / Issue 5 / September 2023
- Published online by Cambridge University Press:
- 08 August 2023, e146
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Women and gender-diverse people with early psychosis are at risk for suboptimal sexual health outcomes, yet little research has explored their sexual health experiences.
AimsThis study explored sexual health experiences and related priorities among women and gender-diverse people with early psychosis, to identify opportunities for improvements in sexual health and well-being.
MethodSemi-structured individual qualitative interviews explored how patient participants (n = 19, aged 18–31 years, cisgender and transgender women and non-binary individuals) receiving clinical care from early psychosis programmes in Ontario, Canada, experienced their sexual health, including sexual function and behaviour. Thematic analysis was conducted, with triangulation from interviews/focus groups with clinicians (n = 36) who provide sexual and mental healthcare for this population.
ResultsThree key themes were identified based on patient interviews: theme 1 was the impact of psychotic illness and its treatments on sexual function and activity, including variable changes in sex drive, attitudes and behaviours during acute psychosis, vulnerability to trauma and medications; theme 2 related to intimacy and sexual relationships in the context of psychosis, with bidirectional effects between relationships and mental health; and theme 3 comprised autonomy, identity and intersectional considerations, including gender, sexuality, culture and religion, which interplay with psychosis and sexual health. Clinicians raised each of these priority areas, but emphasised risk prevention relative to patients’ more holistic view of their sexual health and well-being.
ConclusionsWomen and non-binary people with early psychosis have wide-ranging sexual health priorities, affecting many facets of their lives. Clinical care should incorporate this knowledge to optimise sexual health and well-being in this population.
In-situ Fracture Toughness of Single Crystal Silicon Double-Cantilever Beams
- Sara M. Dickens, Frank W. DelRio, Scott J. Grutzik, William M. Mook, Brad L. Boyce, Eric Hintsala, Douglas Stauffer, Robert F. Cook
-
- Journal:
- Microscopy and Microanalysis / Volume 28 / Issue S1 / August 2022
- Published online by Cambridge University Press:
- 22 July 2022, pp. 14-15
- Print publication:
- August 2022
-
- Article
-
- You have access Access
- Export citation
P.002 Saccade parameters reveal cognitive impairment and differentially associate with cognitive domains across neurodegenerative diseases
- HC Riek, BC Coe, DC Brien, J Huang, A Abrahao, S Arnott, D Beaton, M Binns, S Black, M Borrie, L Casaubon, D Dowlatshahi, E Finger, C Fischer, A Frank, M Freedman, D Grimes, A Hassan, M Jog, S Kumar, D Kwan, A Lang, J Lawrence Dewar, B Levine, W Lou, J Mandzia, C Marras, M Masellis, P McLaughlin, J Orange, S Pasternak, A Peltsch, B Pollock, T Rajji, A Roberts, D Sahlas, G Saposnik, D Seitz, C Shoesmith, T Steeves, S Strother, S Sujanthan, K Sunderland, R Swartz, B Tan, D Tang-Wai, C Tartaglia, A Troyer, J Turnbull, L Zinman, ONDRI Investigators (), DP Munoz
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 49 / Issue s1 / June 2022
- Published online by Cambridge University Press:
- 24 June 2022, p. S8
-
- Article
-
- You have access Access
- Export citation
-
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
Evaluation of a Drama-Based Experiential Learning Group Programme for Multidisciplinary Staff and People With Lived Experience in Psychiatry
- Rupal Dave, Thomas Walker, Hugh Grant-Peterkin, Robert Fisher, Frank Rohricht
-
- Journal:
- BJPsych Open / Volume 8 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 20 June 2022, pp. S2-S3
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Aims
Experiential learning, such as simulation-based training, is widely used in health education. Dramatic self-expression adds another layer through enacted perspective taking, and embodied self-exploration of interaction with others, to foster situated learning. We describe the evaluation of an innovative drama-based experiential learning project involving collaboration between multidisciplinary mental healthcare staff and people with lived experience of mental illness. The programme was facilitated at East London NHS Foundation Trust by a theatre company experienced in delivering workshops with service users. A weekly group programme took place online over 8 weeks during the COVID-19 pandemic and included activities of improvisation, embodied enactments and debriefing. The programme led to co-production of a drama piece that was filmed and distributed online. It was hypothesised that the experiential learning might result in individual benefits for all participants, such as improved well-being and increased mutual understanding of each other's experience of mental health care. The project aimed to improve relationships between healthcare disciplines, and between staff and service users. Additionally, aims were to empower service users, and support staff to practice core interpersonal skills. Objectives of the evaluation were to study the impact of the experiential learning, understand participants’ experience, and explore challenges and benefits.
MethodsA mixed methods approach was taken to evaluate the programme. Following completion of the project, participants were invited to complete a questionnaire utilising a Likert scale rating of overall satisfaction with the project, perceived benefit and impact on specific domains such as working with others. One-to-one semi-structured interviews were conducted according to a topic-guide, and qualitative data were analysed using open & axial coding for thematic analysis.
Results11 participants, including Psychiatrists, Occupational Therapists and current service users, completed the experiential learning and filming. Questionnaire data suggested participants were highly satisfied with the learning and felt it would be valuable to others. Themes include the positive experience of creativity, dismantling of hierarchy, improved empathy, confidence and connection. Potential challenges were digital inequality and lack of dedicated time for professional development.
ConclusionA drama-based experiential learning group programme for healthcare staff and service users is a highly beneficial learning experience. Participants describe changes on a personal level as well as improved understanding of others’ perspectives. This form of experiential learning features collaborative working that aligns with principles of co-production and supports the development of interpersonal skills; the findings suggest that drama-based experiential learning is a useful method in health education to complement knowledge acquisition.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
-
- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
- Print publication:
- August 2022
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
302 Abaloparatide as a novel therapy for posttraumatic osteoarthritis
- Samantha H. Landgrave, Toru Ishii, Robert Maynard, Andrew Wu, Dana Godfrey, Terrin Manes, Veronica Butler, David Villani, Honey Hendesi, Rachel Frank, Srividhya Iyer, Karin Payne, Douglas J. Adams, Lacey Favazzo, Beate Lanske, Michael J. Zuscik
-
- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, p. 53
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
24 - Galois Groups of Composed Schubert Problems
- Edited by Paolo Aluffi, Florida State University, David Anderson, Ohio State University, Milena Hering, University of Edinburgh, Mircea Mustaţă, University of Michigan, Ann Arbor, Sam Payne, University of Texas, Austin
-
- Book:
- Facets of Algebraic Geometry
- Published online:
- 14 March 2022
- Print publication:
- 07 April 2022, pp 336-366
-
- Chapter
- Export citation
Asymptotic identities for additive convolutions of sums of divisors
- ROBERT J. LEMKE OLIVER, SUNROSE T. SHRESTHA, FRANK THORNE
-
- Journal:
- Mathematical Proceedings of the Cambridge Philosophical Society / Volume 174 / Issue 1 / January 2023
- Published online by Cambridge University Press:
- 01 April 2022, pp. 59-78
- Print publication:
- January 2023
-
- Article
- Export citation
-
In a 1916 paper, Ramanujan studied the additive convolution $S_{a, b}(n)$ of sum-of-divisors functions $\sigma_a(n)$ and $\sigma_b(n)$ , and proved an asymptotic formula for it when a and b are positive odd integers. He also conjectured that his asymptotic formula should hold for all positive real a and b. Ramanujan’s conjecture was subsequently proved by Ingham, and then by Halberstam with a power saving error term.
In this paper, we give a new proof of Ramanujan’s conjecture that obtains lower order terms in the asymptotics for most ranges of the parameters. We also describe a connection to a counting problem in geometric topology that was studied in the second author’s thesis and which served as our initial motivation in studying this sum.
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
-
- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
-
- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Mental health emergencies and COVID-19: the impact of ‘lockdown’ in the East Midlands of the UK
- Harriet Elizabeth Moore, Aloysius Niroshan Siriwardena, Mark Gussy, Frank Tanser, Bartholomew Hill, Robert Spaight
-
- Journal:
- BJPsych Open / Volume 7 / Issue 4 / July 2021
- Published online by Cambridge University Press:
- 26 July 2021, e139
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
The most immediate response of the research community to COVID-19 has been a focus on understanding the effects, treatment and prevention of infection. Of equal and ongoing importance is elucidating the impact of mitigation measures, such as lockdown, on the well-being of societies. Research about mental health and lockdown in the UK has predominately involved large surveys that are likely to encounter self-selection bias. Further, self-reporting does not constitute a clinical judgement.
AimsTo (a) compare the age, gender and ethnicity of patients experiencing mental health emergencies prior compared with during lockdown, (b) determine whether the nature of mental health emergencies has changed during compared with before lockdown, (c) explore the utility of emergency medical service data for identifying vulnerability to mental health emergencies in real time during a pandemic.
MethodA total of 32 401 clinical records of ambulance paramedics attending mental health emergencies in the East Midlands of the UK between 23 March and 31 July 2020 and the same period in 2019 were analysed using binary logistic regression.
ResultsPeople of younger age, male gender and South Asian and Black ethnicity are particularly vulnerable to acute mental health conditions during lockdown. Patients with acute cases of anxiety have increased during lockdown whereas suicide and intentional drug overdose have decreased.
ConclusionsSelf-reported data may underrepresent the true impact of lockdown on male mental health and ethnic minority groups. Emergency medical data can be used to identify vulnerable communities in the context of the extraordinary circumstances surrounding the current pandemic, as well as under more ordinary circumstances.
Quantification of Trace-Level Silicon Doping in AlxGa1–xN Films Using Wavelength-Dispersive X-Ray Microanalysis
- Lucia Spasevski, Ben Buse, Paul R. Edwards, Daniel A. Hunter, Johannes Enslin, Humberto M. Foronda, Tim Wernicke, Frank Mehnke, Peter J. Parbrook, Michael Kneissl, Robert W. Martin
-
- Journal:
- Microscopy and Microanalysis / Volume 27 / Issue 4 / August 2021
- Published online by Cambridge University Press:
- 05 July 2021, pp. 696-704
- Print publication:
- August 2021
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Wavelength-dispersive X-ray (WDX) spectroscopy was used to measure silicon atom concentrations in the range 35–100 ppm [corresponding to (3–9) × 1018 cm−3] in doped AlxGa1–xN films using an electron probe microanalyser also equipped with a cathodoluminescence (CL) spectrometer. Doping with Si is the usual way to produce the n-type conducting layers that are critical in GaN- and AlxGa1–xN-based devices such as LEDs and laser diodes. Previously, we have shown excellent agreement for Mg dopant concentrations in p-GaN measured by WDX with values from the more widely used technique of secondary ion mass spectrometry (SIMS). However, a discrepancy between these methods has been reported when quantifying the n-type dopant, silicon. We identify the cause of discrepancy as inherent sample contamination and propose a way to correct this using a calibration relation. This new approach, using a method combining data derived from SIMS measurements on both GaN and AlxGa1–xN samples, provides the means to measure the Si content in these samples with account taken of variations in the ZAF corrections. This method presents a cost-effective and time-saving way to measure the Si doping and can also benefit from simultaneously measuring other signals, such as CL and electron channeling contrast imaging.
Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments
- Isabella Vainieri, Joanna Martin, Anna-Sophie Rommel, Philip Asherson, Tobias Banaschewski, Jan Buitelaar, Bru Cormand, Jennifer Crosbie, Stephen V. Faraone, Barbara Franke, Sandra K. Loo, Ana Miranda, Iris Manor, Robert D. Oades, Kirstin L. Purves, J. Antoni Ramos-Quiroga, Marta Ribasés, Herbert Roeyers, Aribert Rothenberger, Russell Schachar, Joseph Sergeant, Hans-Christoph Steinhausen, Pieter J. Vuijk, Alysa E. Doyle, Jonna Kuntsi
-
- Journal:
- Psychological Medicine / Volume 52 / Issue 14 / October 2022
- Published online by Cambridge University Press:
- 03 February 2021, pp. 3150-3158
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
MethodsThe discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
ResultsWhen combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
ConclusionsWe detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.