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Structural brain correlates of childhood trauma with replication across two large, independent community-based samples
- Rebecca A. Madden, Kimberley Atkinson, Xueyi Shen, Claire Green, Robert F. Hillary, Emma Hawkins, Emma Såge, Anca-Larisa Sandu, Gordon Waiter, Christopher McNeil, Mathew Harris, Archie Campbell, David Porteous, Jennifer A. Macfarlane, Alison Murray, Douglas Steele, Liana Romaniuk, Stephen M. Lawrie, Andrew M. McIntosh, Heather C. Whalley
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- Journal:
- European Psychiatry / Volume 66 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 26 January 2023, e19
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Introduction
Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.
MethodsThe two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.
ResultsChildhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.
DiscussionAssociations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.
Diversity and violence during conflict migration: The Troubles in Northern Ireland
- Claire L. Adida, Joseph M. Brown, Gordon C. McCord, Paul McLachlan
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- Journal:
- Political Science Research and Methods / Volume 11 / Issue 3 / July 2023
- Published online by Cambridge University Press:
- 26 September 2022, pp. 451-467
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Diversity's effect on violence is ambiguous. Some studies find that diverse areas experience more violence; others find the opposite. Yet conflict displaces and intimidates people, creating measurement challenges. We propose a novel indicator of diversity that circumvents these problems: the location of physical structures at disaggregated geographical levels. We introduce this solution in the context of the Troubles in Northern Ireland. Our data reveal a curvilinear relationship between diversity and conflict-related deaths, with the steepest increase at low diversity, driven by an increase in violence when our proxy for the Catholic proportion of the population rises from 0 to 20 percent. These patterns are consistent with a theory of group threat through exposure.
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
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- 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
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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.
Provision of NHS generalist and specialist services to care homes in England: review of surveys
- Steve Iliffe, Susan L. Davies, Adam L. Gordon, Justine Schneider, Tom Dening, Clive Bowman, Heather Gage, Finbarr C. Martin, John R.F. Gladman, Christina Victor, Julienne Meyer, Claire Goodman
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- Journal:
- Primary Health Care Research & Development / Volume 17 / Issue 2 / March 2016
- Published online by Cambridge University Press:
- 05 May 2015, pp. 122-137
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Background
The number of beds in care homes (with and without nurses) in the United Kingdom is three times greater than the number of beds in National Health Service (NHS) hospitals. Care homes are predominantly owned by a range of commercial, not-for-profit or charitable providers and their residents have high levels of disability, frailty and co-morbidity. NHS support for care home residents is very variable, and it is unclear what models of clinical support work and are cost-effective.
ObjectivesTo critically evaluate how the NHS works with care homes.
MethodsA review of surveys of NHS services provided to care homes that had been completed since 2008. It included published national surveys, local surveys commissioned by Primary Care organisations, studies from charities and academic centres, grey literature identified across the nine government regions, and information from care home, primary care and other research networks. Data extraction captured forms of NHS service provision for care homes in England in terms of frequency, location, focus and purpose.
ResultsFive surveys focused primarily on general practitioner services, and 10 on specialist services to care home. Working relationships between the NHS and care homes lack structure and purpose and have generally evolved locally. There are wide variations in provision of both generalist and specialist healthcare services to care homes. Larger care home chains may take a systematic approach to both organising access to NHS generalist and specialist services, and to supplementing gaps with in-house provision. Access to dental care for care home residents appears to be particularly deficient.
ConclusionsHistorical differences in innovation and provision of NHS services, the complexities of collaborating across different sectors (private and public, health and social care, general and mental health), and variable levels of organisation of care homes, all lead to persistent and embedded inequity in the distribution of NHS resources to this population. Clinical commissioners seeking to improve the quality of care of care home residents need to consider how best to provide fair access to health care for older people living in a care home, and to establish a specification for service delivery to this vulnerable population.
Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept
- M. L. Hamshere, E. K. Green, I. R. Jones, L. Jones, V. Moskvina, G. Kirov, D. Grozeva, I. Nikolov, D. Vukcevic, S. Caesar, K. Gordon-Smith, C. Fraser, E. Russell, G. Breen, D. St Clair, D. A. Collier, A. H. Young, I. N. Ferrier, A. Farmer, P. McGuffin, P. A. Holmans, M. J. Owen, M. C. O'Donovan, N. Craddock, Wellcome Trust Case Control Consortium
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- Journal:
- The British Journal of Psychiatry / Volume 195 / Issue 1 / July 2009
- Published online by Cambridge University Press:
- 02 January 2018, pp. 23-29
- Print publication:
- July 2009
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Background
Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological–genetic research.
AimsTo use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case–control bipolar disorder sample.
MethodWe analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM–IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type.
ResultsThe RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42 × 10–7). Biological systems implicated included gamma amniobutyric acid (GABA)A receptors. Genes having at least one associated polymorphism at P<10–4 included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12.
ConclusionsOur findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.
Reactions in Cemented Nuclear Waste forms – the Need for a Toolbox of Different Cement Types
- Neil B Milestone, Yun Bai, Paulo R Borges, Nick C Collier Jean-Phillipe Gorce, Laura E Gordon, Anthony Setiadi, Claire A Utton, Qizhi Zhou
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- Journal:
- MRS Online Proceedings Library Archive / Volume 932 / 2006
- Published online by Cambridge University Press:
- 21 March 2011, 49.1
- Print publication:
- 2006
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Encapsulation of low and intermediate level waste (LLW and ILW) into a monolithic waste form is a key method for preparing such wastes for storage and ultimate disposal. One of the most efficient ways of doing this is by cementation, successfully used for much of today's operational waste in the UK. Formulations are based on composite cements where high levels ofpulverised fuel ash or blast furnace slag replace ordinary Portland cement (OPC). These provide cementing systems with good fluidity, lowered heat of hydration and a matrix with lower porosity and permeability. Further the alkaline hydrated calcium silicate matrix ensures insolubility of many metal hydroxides and hydrated oxides. Dealing with historic or legacy wastes presents a challenge as for many, a suitable cementing formulation has yet to be devised. To achieve ultimate durability, likely interactions between the waste and the cementing matrix need to be well understood when choosing the cement system to be used. The alkaline OPC based matrix causes corrosion with metals such as Al and Mg and porous silicates and layered metal hydroxides used to selectively remove radionucleides react in the alkaline environment, potentially releasing the adsorbed species. Slurries of materials normally considered inert show interactions within the OPC composite systems, although these are not considered detrimental for durability. This paper describes the chemistry of some interactions that occur within OPC composite cements. It also details some results for alternative cementing systems that may provide a toolbox of cement types that may address many of the interaction issues. These include calcium sulphoaluminate cements, inorganic polymers or geopolymers, and activated slag systems.
12 - Anthropometry in the US armed forces
- Edited by Stanley J. Ulijaszek, University of Cambridge, C. G. Nicholas Mascie-Taylor, University of Cambridge
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- Anthropometry
- Published online:
- 19 November 2009
- Print publication:
- 17 February 1994, pp 178-210
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Summary
Military anthropometry in the United States has a long history, beginning at least as early as the Civil War, when such variables as stature, weight, and the body mass index (BMI) were utilized to identify recruits likely to be malnourished, tuberculous, or otherwise unfit for military duty (Ordronaux, 1863). The Civil War surveys also encouraged extensive investigation of the relationships between anthropometry and ancestry, birthplace, physiological measures, disease prevalence, and physical anomalies (Gould, 1869; Baxter, 1875). During World War I (WWI), stature, weight, BMI, pubic height, and chest circumference were utilized as indicators of fitness for load-carrying, marching, and fighting (Davenport & Love, 1921). Indeed, the nature and validity of relations between anthropometry and soldier health and physical performance continue to be a primary focus of military research, and they form the basis of many anthropometric standards for the selection and retention of individual military personnel (Friedl, 1992).
Whereas anthropometric standards for accession, retention, and occupational assignment are by nature applied to the individual soldier, it is the anthropometric variation of military populations as a whole that must be considered in the design and sizing of clothing, protective equipment, workstations, and other military hardware. The first US military survey to specifically address clothing sizing was conducted on approximately 100 000 separatees (soldiers discharged from service) at the end of WWI (Davenport & Love, 1921). By the end of World War II (WWII), gross incompatibilities between body size distributions and the workstations of major military hardware systems (such as the gun turrets of the B-17 bomber aircraft) had fuelled the application of anthropometry in the ever-growing field of human engineering (Brues, 1992).
Soil pH, Bone Preservation, and Sampling Bias at Mortuary Sites
- Claire C. Gordon, Jane E. Buikstra
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- Journal:
- American Antiquity / Volume 46 / Issue 3 / July 1981
- Published online by Cambridge University Press:
- 20 January 2017, pp. 566-571
- Print publication:
- July 1981
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Prediction of human skeletal preservation at mortuary sites is important in archaeological research and in cultural resources management. In this study, correlations between osseous deterioration and soil acidity, as measured by pH, were found to be significant. Age-associated preservation biases were also evident. The use of multiple regression is suggested as a technique for estimating recovery of human osteological remains in archaeological context.