ORCID Profile
0000-0002-1135-4141
Current Organisations
The University of Edinburgh
,
Federation University
,
National Center for Biological Sciences
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Cold Spring Harbor Laboratory
Date: 13-10-2020
DOI: 10.1101/2020.10.08.20205245
Abstract: Low-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 in iduals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.
Publisher: Springer Science and Business Media LLC
Date: 08-12-2020
DOI: 10.1038/S41398-020-01109-5
Abstract: It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent s les comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2022
DOI: 10.1038/S41467-022-32319-8
Abstract: Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed ( N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits ( N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2019
DOI: 10.1038/S41380-019-0605-Z
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small s le sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 in iduals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippoc us, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of in idual CpGs revealed genome-wide significant associations with hippoc al volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippoc al volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Publisher: Springer Science and Business Media LLC
Date: 19-11-2020
DOI: 10.1038/S42003-020-01422-1
Abstract: The malaria parasite Plasmodium obligatorily infects and replicates inside hepatocytes surrounded by a parasitophorous vacuole membrane (PVM), which is decorated by the host-cell derived autophagy protein LC3. We have previously shown that the parasite-derived, PVM-resident protein UIS3 sequesters LC3 to avoid parasite elimination by autophagy from hepatocytes. Here we show that a small molecule capable of disrupting this interaction triggers parasite elimination in a host cell autophagy-dependent manner. Molecular docking analysis of more than 20 million compounds combined with a phenotypic screen identified one molecule, C4 (4-{[4-(4-{5-[3-(trifluoromethyl) phenyl]-1,2,4-oxadiazol-3-yl}benzyl)piperazino]carbonyl}benzonitrile), capable of impairing infection. Using biophysical assays, we established that this impairment is due to the ability of C4 to disrupt UIS3–LC3 interaction, thus inhibiting the parasite’s ability to evade the host autophagy response. C4 impacts infection in autophagy-sufficient cells without harming the normal autophagy pathway of the host cell. This study, by revealing the disruption of a critical host–parasite interaction without affecting the host’s normal function, uncovers an efficient anti-malarial strategy to prevent this deadly disease.
Publisher: Springer Science and Business Media LLC
Date: 10-2021
DOI: 10.1186/S12992-021-00768-3
Abstract: The current pandemic of COVID-19 impacted the psychological wellbeing of populations globally. We aimed to examine the extent and identify factors associated with psychological distress, fear of COVID-19 and coping. We conducted a cross-sectional study across 17 countries during Jun-2020 to Jan-2021. Levels of psychological distress (Kessler Psychological Distress Scale), fear of COVID-19 (Fear of COVID-19 Scale), and coping (Brief Resilient Coping Scale) were assessed. A total of 8,559 people participated mean age (±SD) was 33(±13) years, 64% were females and 40% self-identified as frontline workers. More than two-thirds (69%) experienced moderate-to-very high levels of psychological distress, which was 46% in Thailand and 91% in Egypt. A quarter (24%) had high levels of fear of COVID-19, which was as low as 9% in Libya and as high as 38% in Bangladesh. More than half (57%) exhibited medium to high resilient coping the lowest prevalence (3%) was reported in Australia and the highest (72%) in Syria. Being female (AOR 1.31 [95% CIs 1.09-1.57]), perceived distress due to change of employment status (1.56 [1.29-1.90]), comorbidity with mental health conditions (3.02 [1.20-7.60]) were associated with higher levels of psychological distress and fear. Doctors had higher psychological distress (1.43 [1.04-1.97]), but low levels of fear of COVID-19 (0.55 [0.41-0.76]) nurses had medium to high resilient coping (1.30 [1.03-1.65]). The extent of psychological distress, fear of COVID-19 and coping varied by country however, we identified few higher risk groups who were more vulnerable than others. There is an urgent need to prioritise health and well-being of those people through well-designed intervention that may need to be tailored to meet country specific requirements.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2020
DOI: 10.1038/S41467-020-18367-Y
Abstract: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery s le comprises 22,824 in iduals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Publisher: MDPI AG
Date: 02-2022
Abstract: The use of electronic cigarettes or vaping is currently increasing in popularity globally. Debate continues regarding their potential role for smoking cessation. We aimed to compare the profiles, use and perceptions of using e-cigarettes amongst online forum users in a developed and a developing country. A cross-sectional survey was conducted among members of different popular online forums in Australia and Bangladesh who were current or ex-users of e-cigarettes. There were 422 study participants, 261 (62%) from Australia and 161 (38%) from Bangladesh. The mean age was 36.3 (±12) years and 83% were men. Australians were more likely to be exclusive users of e-cigarettes (70% vs. 30%, AOR 3.05 [95% CI 1.63–5.71]), but less likely to be dual users of smoking and e-cigarettes (43% vs. 57%, 0.36 [0.19–0.69]) they were also more likely to mention that the perceived reasons for using were their low cost, good taste/flavour, safety and assistance in reducing or quitting smoking (66% vs. 34%, 5.10 [2.04–12.8]), but less likely to mention a social/cool image as a reason for use (23% vs. 77%, 0.11 [0.01–0.87]) compared with Bangladeshi participants. About two-thirds of the participants in both countries perceived the use of e-cigarettes as less addictive than cigarettes and more than three-quarters perceived them as less harmful. E-cigarette users in Australia were more likely to use them to reduce or quit cigarettes compared with those in Bangladesh, and dual use was common in Bangladesh. These findings warrant the consideration of precautions for promoting e-cigarettes as a harm reduction strategy for smoking cessation in developing countries, such as Bangladesh.
Publisher: SAGE Publications
Date: 23-06-2021
DOI: 10.1177/10436596211026373
Abstract: In the past decade, there has been an influx of migrant nurses from India to Australia. Migrant professionals have specific transition needs associated with working in Mental Health (MH). This study aimed to explore the transition experience of overseas trained nurses from India working in Australian MH settings. Hermeneutic phenomenology was the methodological approach used in the study. The participants ( N = 16) were overseas trained nurses from India. Data were collected through in-depth interview and analysed using thematic analysis. The findings resulted in the identification of the following themes: (1) Living in dual culture, (2) Loneliness, (3) Discrimination, and (4) Feeling incomplete. It is evident that the transition to work in MH in Australia was a journey of mixed experiences. While certain findings of this study are comparable with experiences of migrant nurses in other settings, it provides insight into those that are working in MH.
Publisher: SAGE Publications
Date: 03-06-2022
DOI: 10.1177/10664807221104133
Abstract: The primary aim of the literature review is to explore the relevant literature on the use and effectiveness of genograms in family therapy. The literature is predominantly related to the use of genograms in various settings and adaptations. There are minimal studies on the effectiveness of genograms as a therapeutic tool in family therapy. Searches were conducted of MEDLINE, EMBASE, CINAHL, SCOPUS and PsycINFO electronic databases. The international review includes all studies, irrespective of study methodology. This review will inform clinicians working in family therapy and other relevant disciplines on the usefulness of genograms as a therapeutic tool, ex les of adaptations to the traditional genogram for specific populations and purposes, and, to a lesser extent, the therapeutic effectiveness of genograms in family therapy. The results and discussion will provide insights on the utilisation of genograms, the range of population, gaps in the existing literature and the need for further research.
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1038/S41593-022-01042-4
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 in iduals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-03-2020
Abstract: The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 in iduals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. We identified 369 nominally genome-wide significant loci ( P 5 × 10 −8 ) associated with cortical structure in a discovery s le of 33,992 participants of European ancestry. Of the 360 loci for which replication data were available, 241 loci influencing surface area and 66 influencing thickness remained significant after replication, with 237 loci passing multiple testing correction ( P 8.3 × 10 −10 187 influencing surface area and 50 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness surface area and thickness showed a negative genetic correlation ( r G = −0.32, SE = 0.05, P = 6.5 × 10 −12 ), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain s les, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on in idual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 46 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function. ( A ) Measurement of cortical surface area and thickness from MRI. ( B ) Genomic locations of common genetic variants that influence global and regional cortical structure. ( C ) Our results support the radial unit hypothesis that the expansion of cortical surface area is driven by proliferating neural progenitor cells. ( D ) Cortical surface area shows genetic correlation with psychiatric and cognitive traits. Error bars indicate SE. IMAGE CREDITS: (A) K. COURTNEY (C) M. R. GLASS
Publisher: Springer Science and Business Media LLC
Date: 28-05-2020
DOI: 10.1038/S41380-020-0774-9
Abstract: Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI ( n = 6420) and genetic data ( n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.
Publisher: Hindawi Limited
Date: 11-2022
DOI: 10.1111/JONM.13882
Abstract: This review aims to identify the factors influencing the transition and retention of mental health nurses during the initial years of practice, recognize gaps in the literature and propose evidence-based strategies. Mental health is a challenging specialty recruitment, transition and retention of mental health nurses are known issues of concern. The present study undertakes a scoping review to identify factors influencing the transition and retention of mental health nurses during the initial years of practice and the gaps in that research domain. A literature search was conducted using electronic databases. To gain an understanding of the topic of interest, the review of the literature extended from 2000 to 2022. Existing evidence focuses on specific perspectives of transition. There is limited literature on factors influencing transition and retention among mental health nurses. Findings suggested that personal and professional factors could influence the transition and retention of mental health nurses during the initial years of practice. The main themes identified were personal attributes and professional factors with a number of subthemes. The scoping review identified only a few studies, which showed personal and professional factors related to the transition and retention of mental health nurses at the early stages of their career. Potential benefits of effective transition and support with the understanding of factors influencing transition and retention of early career mental health nurses will enhance staff morale, sustainability of the workforce and better patient outcomes. Additionally, a few recommendations for nurse managers and leaders to improve transitional experiences and retention of early career nurses are highlighted.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2019
Publisher: Springer Science and Business Media LLC
Date: 22-06-2021
Publisher: Cambridge University Press (CUP)
Date: 2022
DOI: 10.1017/GMH.2022.35
Abstract: Healthcare workers (HCWs) have been impacted psychologically due to their professional responsibilities over the prolonged era of the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to identify the predictors of psychological distress, fear, and coping during the COVID-19 pandemic among HCWs. A cross-sectional online survey was conducted among self-identified HCWs across 14 countries (12 from Asia and two from Africa). The Kessler Psychological Distress Scale, the Fear of COVID-19 Scale, and the Brief Resilient Coping Scale were used to assess the psychological distress, fear, and coping of HCWs, respectively. A total of 2447 HCWs participated 36% were doctors, and 42% were nurses, with a mean age of 36 (±12) years, and 70% were females. Moderate to very-high psychological distress was prevalent in 67% of the HCWs the lowest rate was reported in the United Arab Emirates (1%) and the highest in Indonesia (16%). The prevalence of high levels of fear was 20% the lowest rate was reported in Libya (9%) and the highest in Egypt (32%). The prevalence of medium-to-high resilient coping was 63% the lowest rate was reported in Libya (28%) and the highest in Syria (76%). COVID-19 has augmented the psychological distress among HCWs. Factors identified in this study should be considered in managing the wellbeing of HCWs, who had been serving as the frontline drivers in managing the crisis successfully across all participating countries. Furthermore, interventions to address their psychological distress should be considered.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mathew Harris.