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| 2. |
- Gould, Rebecca, et al.
(författare)
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Acceptance and Commitment Therapy for people living with motor neuron disease : an uncontrolled feasibility study
- 2023
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Ingår i: Pilot and Feasibility Studies. - : Springer Nature. - 2055-5784. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND.Methods: PlwMND aged >= 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (>= 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (>= 70% completing >= 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months.Results: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended >= 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status.Conclusions: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway.
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| 3. |
- Abrahamsson, Dimitri, et al.
(författare)
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In Silico Structure Predictions for Non-targeted Analysis : From Physicochemical Properties to Molecular Structures
- 2022
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Ingår i: Journal of the American Society for Mass Spectrometry. - : American Chemical Society (ACS). - 1044-0305 .- 1879-1123. ; 33:7, s. 1134-1147
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Tidskriftsartikel (refereegranskat)abstract
- While important advances have been made in high-resolution mass spectrometry (HRMS) and its applications in non-targeted analysis (NTA), the number of identified compounds in biological and environmental samples often does not exceed 5% of the detected chemical features. Our aim was to develop a computational pipeline that leverages data from HRMS but also incorporates physicochemical properties (equilibrium partition ratios between organic solvents and water; Ksolvent–water) and can propose molecular structures for detected chemical features. As these physicochemical properties are often sufficiently different across isomers, when put together, they can form a unique profile for each isomer, which we describe as the “physicochemical fingerprint”. In our study, we used a comprehensive database of compounds that have been previously reported in human blood and collected their Ksolvent–water values for 129 partitioning systems. We used RDKit to calculate the number of RDKit fragments and the number of RDKit bits per molecule. We then developed and trained an artificial neural network, which used as an input the physicochemical fingerprint of a chemical feature and predicted the number and types of RDKit fragments and RDKit bits present in that structure. These were then used to search the database and propose chemical structures. The average success rate of predicting the right chemical structure ranged from 60 to 86% for the training set and from 48 to 81% for the testing set. These observations suggest that physicochemical fingerprints can assist in the identification of compounds with NTA and substantially improve the number of identified compounds.
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| 4. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
- Gould, Rebecca L., et al.
(författare)
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A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND) : study protocol
- 2022
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Ingår i: BMC Neurology. - : Springer Nature. - 1471-2377. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2-3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health.Aims: To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND.Methods: The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged >= 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling.Discussion: This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND.
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| 6. |
- Jin, Guangfu, et al.
(författare)
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Genome-wide Association Study Identifies Loci at ATF7IP and KLK2 Associated with Percentage of Circulating Free PSA
- 2013
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Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 15:1, s. 95-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. MATERIALS/METHODS: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P < 10(-5) were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. RESULTS: We identified two loci that were associated with %fPSA at a genome-wide significance level (P < 5 x 10(-8)). The first associated SNP was rs3213764 (P = 6.45 x 10(-10)), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P = .015). The second locus was rs1354774 (P = 1.25 x 10(-12)), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. CONCLUSIONS: These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA.
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| 7. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 8. |
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| 9. |
- Weeks, Kirsty R, et al.
(författare)
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Needs and preferences for psychological interventions of people with motor neuron disease.
- 2019
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 20:7-8, s. 521-531
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a lack of knowledge about what factors may impede or facilitate engagement in psychological interventions in people with motor neuron disease (pwMND) and how such interventions can be adapted to best meet the needs of this population.Objectives: To explore the needs and preferences of pwMND with respect to psychological interventions, and how best to adapt such interventions for pwMND.Methods: A series of semi-structured interviews (n = 22) and workshops (n = 3) were conducted with pwMND (n = 15), informal caregivers of pwMND (n = 10), and MND healthcare professionals (n = 12). These explored preferences and concerns that would need to be considered when delivering a psychological intervention for pwMND. Three areas were explored: (i) perceived factors that may hinder or facilitate pwMND engaging with psychological interventions; (ii) ways in which such interventions could be adapted to meet the individual needs of pwMND; and (iii) views regarding the main psychological issues that would need to be addressed. Workshops and interviews were audio recorded and transcribed and thematic analysis was used to inductively derive themes.Findings: Data could be classified within four overarching themes: unfamiliar territory; a series of losses; variability and difficulty meeting individual needs; and informal support.Conclusions: Flexibility, tailoring interventions to the individual needs of pwMND, and encouraging autonomy are key attributes for psychological interventions with pwMND. Psychological interventions such as Acceptance and Commitment Therapy (ACT) could be acceptable for pwMND if adapted to their specific needs.
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