المؤلفون: Al-Diwani, A, Theorell, J, Damato, V, Bull, J, McGlashan, N, Green, E, Kienzler, AK, Harrison, R, Hassanali, T, Campo, L, Browne, M, Easton, A, Majd, HS, Tenaka, K, Iorio, R, Dale, RC, Harrison, P, Geddes, J, Quested, D, Sharp, D, Lee, ST, Nauen, DW, Makuch, M, Lennox, B, Fowler, D, Sheerin, F, Waters, P, Leite, MI, Handel, AE, Irani, SR

المصدر: Brain : a journal of neurology. 145(8):2742-2754

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:149759312Test

المؤلفون: Pagnamenta, A.T., Yu, J., Walker, S., Noble, A.J., Lord, J., Dutta, P., Hashim, M., Camps, C., Green, H., Devaiah, S., Nashef, L., Parr, J., Fratter, C., Ibnouf Hussein, R., Lindsay, S.J., Lalloo, F., Banos-Pinero, B., Evans, D., Mallin, L., Waite, A., Evans, J., Newman, A., Allen, Z., Perez-Becerril, C., Ryan, G., Hart, R., Taylor, J., Bedenham, T., Clement, E., Blair, E., Hay, E., Forzano, F., Higgs, J., Canham, N., Majumdar, A., McEntagart, M., Lahiri, N., Stewart, H., Smithson, S., Calpena, E., Jackson, A., Banka, S., Titheradge, H., McGowan, R., Rankin, J., Shaw-Smith, C., Evans, D.G., Burghel, G.J., Smith, M.J., Anderson, E., Madhu, R., Firth, H., Ellard, S., Brennan, P., Anderson, C., Taupin, D., Rogers, M.T., Cook, J.A., Durkie, M., East, J.E., Fowler, D., Wilson, L., Igbokwe, R., Gardham, A., Tomlinson, I., Baralle, D., Uhlig, H.H., Taylor, J.C.

الوصف: Detection of structural variants (SVs) is currently biased toward those that alter copy number. The relative contribution of inversions toward genetic disease is unclear. In this study, we analyzed genome sequencing data for 33,924 families with rare disease from the 100,000 Genomes Project. From a database hosting >500 million SVs, we focused on 351 genes where haploinsufficiency is a confirmed disease mechanism and identified 47 ultra-rare rearrangements that included an inversion (24 bp to 36.4 Mb, 20/47 de novo). Validation utilized a number of orthogonal approaches, including retrospective exome analysis. RNA-seq data supported the respective diagnoses for six participants. Phenotypic blending was apparent in four probands. Diagnostic odysseys were a common theme (>50 years for one individual), and targeted analysis for the specific gene had already been performed for 30% of these individuals but with no findings. We provide formal confirmation of a European founder origin for an intragenic MSH2 inversion. For two individuals with complex SVs involving the MECP2 mutational hotspot, ambiguous SV structures were resolved using long-read sequencing, influencing clinical interpretation. A de novo inversion of HOXD11-13 was uncovered in a family with Kantaputra-type mesomelic dysplasia. Lastly, a complex translocation disrupting APC and involving nine rearranged segments confirmed a clinical diagnosis for three family members and resolved a conundrum for a sibling with a single polyp. Overall, inversions play a small but notable role in rare disease, likely explaining the etiology in around 1/750 families across heterogeneous clinical cohorts.

وصف الملف: text

العلاقة: https://eprints.whiterose.ac.uk/214063/1/The%20impact%20of%20inversions%20across%2033,924%20families%20with%20rare%20disease%20from%20a%20national%20genome%20sequencing%20project.pdfTest; Pagnamenta, A.T. orcid.org/0000-0001-7334-0602 , Yu, J., Walker, S. et al. (65 more authors) (2024) The impact of inversions across 33,924 families with rare disease from a national genome sequencing project. The American Journal of Human Genetics, 111 (6). pp. 1140-1164. ISSN 0002-9297

الإتاحة: https://eprints.whiterose.ac.uk/214063Test/
https://eprints.whiterose.ac.uk/214063/1/The%20impact%20of%20inversions%20across%2033,924%20families%20with%20rare%20disease%20from%20a%20national%20genome%20sequencing%20project.pdfTest

المؤلفون: Wu, W, Rieger, S, Baxter, L, Adams, E, Andersson, J, Cobo, M, Andritsou, F, Bastiani, M, Fry, RE, Frost, R, Fitzgibbon, S, Fowler, D, Gallagher, C, Howard, A, Hajnal, J, Moultrie, F, Monk, V, Poster, D, Papp, D, Price, A, Sallet, J, Sanders, M, Wilkinson, D, Slater, R, Miller, K

الوصف: Diffusion MRI of the infant brain allows investigation of the organizational structure of maturing fibers during brain development. Post-mortem imaging has the potential to achieve high resolution by using long scan times, enabling precise assessment of small structures. Technical development for post-mortem diffusion MRI has primarily focused on scanning of fixed tissue, which is robust to effects like temperature drift that can cause unfixed tissue to degrade. The ability to scan unfixed tissue in the intact body would enable post-mortem studies without organ donation, but poses new technical challenges. This paper describes our approach to scan setup, protocol optimization, and tissue protection in the context of the Developing Human Connectome Project (dHCP) of neonates. A major consideration was the need to preserve the integrity of unfixed tissue during scanning in light of energy deposition at ultra-high magnetic field strength. We present results from one of the first two subjects recruited to the study, who died on postnatal day 46 at 29+6 weeks postmenstrual age, demonstrating high-quality diffusion MRI data. We find altered diffusion properties consistent with post-mortem changes reported previously. Preliminary voxel-wise and tractography analyses are presented with comparison to age-matched in vivo dHCP data. These results show that high-quality, high-resolution post-mortem data of unfixed tissue can be acquired to explore the developing human

العلاقة: https://ora.ox.ac.uk/objects/uuid:b8f87775-16b5-47bc-9e63-f9038e382be4Test; https://doi.org/10.1162/imag_a_00069Test

الإتاحة: https://doi.org/10.1162/imag_a_00069Test
https://ora.ox.ac.uk/objects/uuid:b8f87775-16b5-47bc-9e63-f9038e382be4Test

المؤلفون: Berry, C., Baloc, A-I., Fowler, D., Jones, A-M., Hazell, C.M., Hayward, M.

مصطلحات موضوعية: Psychiatry and Mental health

الوصف: Background Voice-hearing is a common, phenomenologically diverse, experience across different mental health diagnoses. Patient preferences for psychological therapies are helpful in informing treatment commissioning and provision, especially in the context of complex and variable experiences like voice-hearing. There is, however, very limited evidence as to the psychological therapy preferences of transdiagnostic voice-hearers. Methods Three-hundred and thirty-five voice hearers were recruited from secondary care NHS mental health services across England, between 2020 and 2022. Participants completed a questionnaire battery, involving a psychological therapy preference survey. Participants ranked their preferences across categories of practical, technical and relational therapy elements. Therapy preferences were examined using non-parametric ANOVAs and the significance of pairwise comparisons between different therapy elements. Results There were significant differences in all categories of preference elements. Clear hierarchies of preference were observed in therapy location, timing, delivery, and therapy approach. Preferences were evident, albeit with less clear vertical hierarchies, for number of sessions, mode, therapist qualities, and therapy focus, tasks and outcomes. Discussion Overall, participants expressed a preference for individual, face-to-face intervention of at least nine sessions, with a highly experienced therapist and a core focus on enhancing coping strategies for voice-hearing experiences.

وصف الملف: application/pdf

العلاقة: https://westminsterresearch.westminster.ac.uk/download/bd728ebe6bf0b887bec92f1f8c79812e72e39a96619cefa625d6b8da3a1fadc2/1832989/The%20psychological%20therapy%20preferences%20of%20patients%20who%20hear%20voices.pdfTest; https://doi.org/10.1080/17522439.2022.2095000Test; Berry, C., Baloc, A-I., Fowler, D., Jones, A-M., Hazell, C.M. and Hayward, M. 2023. The psychological therapy preferences of patients who hear voices. Psychosis. 15 (1), pp. 1-16. https://doi.org/10.1080/17522439.2022.2095000Test

الإتاحة: https://doi.org/10.1080/17522439.2022.2095000Test
https://westminsterresearch.westminster.ac.uk/item/vyxyw/the-psychological-therapy-preferences-of-patients-who-hear-voicesTest
https://westminsterresearch.westminster.ac.uk/download/bd728ebe6bf0b887bec92f1f8c79812e72e39a96619cefa625d6b8da3a1fadc2/1832989/The%20psychological%20therapy%20preferences%20of%20patients%20who%20hear%20voices.pdfTest

المؤلفون: Peters, E, Hardy, A, Dudley, R, Varese, F, Greenwood, K, Steel, C, Emsley, R, Keen, N, Bowe, S, Swan, S, Underwood, R, Longden, E, Byford, S, Potts, L, Heslin, M, Grey, N, Turkington, D, Fowler, D, Kuipers, E, Morrison, A

الوصف: Background People with psychosis have high rates of trauma, with a post-traumatic stress disorder (PTSD) prevalence rate of approximately 15%, which exacerbates psychotic symptoms such as delusions and hallucinations. Pilot studies have shown that trauma-focused (TF) psychological therapies can be safe and effective in such individuals. This trial, the largest to date, will evaluate the clinical effectiveness of a TF therapy integrated with cognitive behaviour therapy for psychosis (TF-CBTp) on post-traumatic stress symptoms in people with psychosis. The secondary aims are to compare groups on cost-effectiveness; ascertain whether TF-CBTp impacts on a range of other meaningful outcomes; determine whether therapy effects endure; and determine acceptability of the therapy in participants and therapists. Methods Rater-blind, parallel arm, pragmatic randomised controlled trial comparing TF-CBTp + treatment as usual (TAU) to TAU only. Adults (N = 300) with distressing post-traumatic stress and psychosis symptoms from five mental health Trusts (60 per site) will be randomised to the two groups. Therapy will be manualised, lasting 9 months (m) with trained therapists. We will assess PTSD symptom severity (primary outcome); percentage who show loss of PTSD diagnosis and clinically significant change; psychosis symptoms; emotional well-being; substance use; suicidal ideation; psychological recovery; social functioning; health-related quality of life; service use, a total of four times: before randomisation; 4 m (mid-therapy); 9 m (end of therapy; primary end point); 24 m (15 m after end of therapy) post-randomisation. Four 3-monthly phone calls will be made between 9 m and 24 m assessment points, to collect service use over the previous 3 months. Therapy acceptability will be assessed through qualitative interviews with participants (N = 35) and therapists (N = 5–10). An internal pilot will ensure integrity of trial recruitment and outcome data, as well as therapy protocol safety and adherence. Data will be analysed ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:0f969467-f31d-4743-8dcc-595f045ffc3aTest; https://doi.org/10.1186/s13063-022-06215-xTest

الإتاحة: https://doi.org/10.1186/s13063-022-06215-xTest
https://ora.ox.ac.uk/objects/uuid:0f969467-f31d-4743-8dcc-595f045ffc3aTest

المؤلفون: Pinho-Gomes, AC, Roaf, E, Fuller, G, Fowler, D, Lewis, A, ApSimon, H, Noakes, C, Johnstone, P, Holgate, S

المصدر: The Lancet Planetary Health , 7 (9) e727-e728. (2023)

مصطلحات موضوعية: Climate Change, Air Pollution

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10176847/1/Pinho-Gomes_1-s2.0-S2542519623001894-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10176847Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10176847/1/Pinho-Gomes_1-s2.0-S2542519623001894-main.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10176847Test/

المؤلفون: Griffiths, SL, Bogatsu, T, Longhi, M, Butler, E, Alexander, B, Bandawar, M, Everard, L, Jones, PB, Fowler, D, Hodgekins, J, Amos, T, Freemantle, N, McCrone, P, Singh, SP, Birchwood, M, Upthegrove, R

المصدر: Social Psychiatry and Psychiatric Epidemiology (2023) (In press).

مصطلحات موضوعية: Deprivation, Early psychosis, Ethnicity, Inequities, Outcomes

الوصف: PURPOSE: Psychosis disproportionally affects ethnic minority groups in high-income countries, yet evidence of disparities in outcomes following intensive early intervention service (EIS) for First Episode Psychosis (FEP) is less conclusive. We investigated 5-year clinical and social outcomes of young people with FEP from different racial groups following EIS care. METHOD: Data were analysed from the UK-wide NIHR SUPEREDEN study. The sample at baseline (n = 978) included White (n = 750), Black (n = 71), and Asian (n = 157) individuals, assessed during the 3 years of EIS, and up to 2 years post-discharge (n = 296; Black [n = 23]; Asian [n = 52] and White [n = 221]). Outcome trajectories were modelled for psychosis symptoms (positive, negative, and general), functioning, and depression, using linear mixed effect models (with random intercept and slopes), whilst controlling for social deprivation. Discharge service was also explored across racial groups, 2 years following EIS. RESULTS: Variation in linear growth over time was accounted for by racial group status for psychosis symptoms—positive (95% CI [0.679, 1.235]), negative (95% CI [0.315, 0.783]), and general (95% CI [1.961, 3.428])—as well as for functioning (95% CI [11.212, 17.677]) and depressive symptoms (95% CI [0.261, 0.648]). Social deprivation contributed to this variance. Black individuals experienced greater levels of deprivation (p < 0.001, 95% CI [0.187, 0.624]). Finally, there was a greater likelihood for Asian (OR = 3.04; 95% CI [2.050, 4.498]) and Black individuals (OR = 2.47; 95% CI [1.354, 4.520]) to remain in secondary care by follow-up. CONCLUSION: Findings suggest variations in long-term clinical and social outcomes following EIS across racial groups; social deprivation contributed to this variance. Black and Asian individuals appear to make less improvement in long-term recovery and are less likely to be discharged from mental health services. Replication is needed in large, complete data, to fully understand disparities and blind spots ...

وصف الملف: application/pdf

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10164929/1/s00127-023-02428-w.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10164929Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10164929/1/s00127-023-02428-w.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10164929Test/

المؤلفون: Pinho-Gomes, A.-C., Roaf, E., Fuller, G., Fowler, D., Lewis, A., ApSimon, H., Noakes, C., Johnstone, P., Holgate, S.

وصف الملف: text

العلاقة: https://eprints.whiterose.ac.uk/203783/1/1-s2.0-S2542519623001894-main.pdfTest; Pinho-Gomes, A.-C., Roaf, E., Fuller, G. et al. (6 more authors) (2023) Air pollution and climate change. The Lancet Planetary Health, 7 (9). e727-e728. ISSN 2542-5196

الإتاحة: https://eprints.whiterose.ac.uk/203783Test/
https://eprints.whiterose.ac.uk/203783/1/1-s2.0-S2542519623001894-main.pdfTest

المؤلفون: Stevens, C. J., Bell, J. N. B., Brimblecombe, P., Clark, C. M., Dise, N. B., Fowler, D., Lovett, G. M., Wolseley, P. A.

المصدر: Philosophical Transactions: Mathematical, Physical and Engineering Sciences, 2020 Oct . 378(2183), 1-18.

الوصول الحر: https://www.jstor.org/stable/27101034Test

المؤلفون: Frawley, E, Cowman, M, Cella, M, Cohen, D, Ryan, E, Hallahan, B, Bowie, C, McDonald, C, Fowler, D, Wykes, T, Donohoe, G

الوصف: Background Psychosis, even in its early stages, is associated with significant disability, causing it to be ranked ahead of paraplegia and blindness in those aged 18–35 in terms of years lived with disability. Current pharmacological and psychological interventions intervention have focused primarily on the reduction of positive symptoms (hallucinations and delusions), with little benefit to domains of psychosis such as cognitive difficulties and social and occupational functioning. Methods/design The CReSt-R intervention trial is a single center, pilot randomised controlled study based at the National University of Ireland (NUI), Galway. The trial will recruit participants from four clinical sites with assessment and intervention completed by the primary NUI Galway team. The trial will explore the feasibility, acceptability, and effectiveness of a novel psychosocial intervention for early psychosis based on a combined cognitive remediation training and cognitive behavioural therapy approach focused on social recovery. Participants, aged 16–35 within the first 5 years of a diagnosed psychotic disorder, will be recruited from the Children and Adolescent Mental Health Service and the Adult Mental Health Services in the region. Discussion Cognitive remediation training (for improving cognition) and social recovery focused cognitive behavioural therapy, have both separately demonstrated effectiveness. This trial will evaluate the feasibility, acceptability, and explore the efficacy of a treatment approach that combines both approaches as part of an integrated, multicomponent intervention.

وصف الملف: application/pdf

العلاقة: http://sro.sussex.ac.uk/id/eprint/108480/1/Cognitive%20Remediation%20and%20Social%20Recovery%20in%20Early%20Psychosis%20%28CReSt-R%29%20protocol%20for%20a%20pilot%20randomised%20controlled%20study.pdfTest; Frawley, E, Cowman, M, Cella, M, Cohen, D, Ryan, E, Hallahan, B, Bowie, C, McDonald, C, Fowler, D, Wykes, T and Donohoe, G (2022) Cognitive remediation and social recovery in early psychosis (CReSt-R): protocol for a pilot randomised controlled study. Pilot and Feasibility Studies, 8. 109 1-10. ISSN 2055-5784

الإتاحة: https://doi.org/10.1186/s40814-022-01064-6Test
http://sro.sussex.ac.uk/id/eprint/108480Test/
http://sro.sussex.ac.uk/id/eprint/108480/1/Cognitive%20Remediation%20and%20Social%20Recovery%20in%20Early%20Psychosis%20%28CReSt-R%29%20protocol%20for%20a%20pilot%20randomised%20controlled%20study.pdfTest