Publications by authors named "Peter Watson"

437 Publications

Finding the Value in Biobanks: Enhancing the CTRNet Locator.

Biopreserv Biobank 2021 Jul 12. Epub 2021 Jul 12.

Office of Biobank Education and Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Biobanks are a critical piece of Research Infrastructure (RI). However, biobanks need to accept the reality of a life cycle for RIs. Until recently, strategies to sustain biobanks have been commonly focused on ways to maintain current operational models. However, sustaining biobanks as they exist today may be increasingly challenging in the face of the disruption in health and research priorities caused by the COVID-19 pandemic. In this opinion article, we review the current and emerging future drivers of biobank value for their researchers, institutions, and funders, highlighting utilization and impact of research performed using the biobank as key measures of future value. While biobanks can only indirectly influence the specific impact of the research performed, they can transform themselves to more actively redefine utilization to their advantage. Utilization means more than the balance of samples and data in versus out. Utilization means redirecting expertise to best support end users, and importantly, closing the operating gap between biobanks and their end users who seek to find the right biospecimens and data to pursue their research. We discuss the specific role of locators (those created by public investment) in closing this gap and the need for additional tools for researchers, before and subsequent to connecting with locators. For the former, we specifically propose that more support is needed to assist researchers in the decision as to how to best obtain biospecimens and navigate the options as to whether finding existing biospecimens and data held by a biobank is the optimal solution for a given project, or whether the optimal solution is either contracting with a biobank to collect samples or creating a new biobank. We believe this type of biospecimen navigator platform will help to maximize utilization of current biobank resources, and also promote the services and expertise in biobanks to better serve researchers' needs.
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http://dx.doi.org/10.1089/bio.2021.0043DOI Listing
July 2021

Building Research Support Capacity across Human Health Biobanks during the COVID-19 Pandemic.

Biomark Insights 2021 14;16:11772719211024100. Epub 2021 Jun 14.

New South Wales Health Statewide Biobank, New South Wales Health Pathology, Camperdown, NSW, Australia.

Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of biobanking has existed for over 20 years and is supported by several international professional societies and dedicated academic journals. However, despite both rising research demand for human biospecimens, and the growth of biobanking as an academic discipline, many individual biobanks continue to experience sustainability challenges. This commentary will summarize how the COVID-19 pandemic is creating new challenges and opportunities for both the health biobanking sector and the supporting discipline of biobanking. While the challenges for biobanks may be numerous and acute, there are opportunities for both individual biobanks and the discipline of biobanking to embrace change such that biobanks can continue to support and drive biomedical research. We will therefore describe numerous practical steps that individual biobanks and/or the discipline of biobanking can take to survive and possibly thrive in response to the COVID-19 pandemic.
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http://dx.doi.org/10.1177/11772719211024100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207259PMC
June 2021

Vignettes to Illustrate the Value of Tumor Biobanks in Cancer Research in Canada.

Biopreserv Biobank 2021 Jun 24. Epub 2021 Jun 24.

Office of Biobank Education and Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Tumor biobanks are a common research infrastructure. As a collection of biospecimens and annotated data collected to support a multitude of research projects, biobanks facilitate access to materials that are the critical fuel for the generation of data in up to 40% of cancer research publications. However, quantifying how to measure biobanks' impact and their value on the field of cancer research discoveries and findings, has not been well elucidated. We have used a qualitative case study approach to illustrate the impact of tumor biobanks. We assessed the impact of three research studies published between 2010 and 2012 that required easily accessible "classic" biobanks. Each study utilized preassembled collections of tumor biospecimens with associated patient outcomes data at the outset of the research project. We compared the resulting journal impact factor, altmetric and field-weighted citation impact factor scores for each article to a set of six "benchmark" articles that represent cancer research and treatment discoveries from the same time period and two sentinel scientific discovery articles. We developed a value model using a literature search and design-thinking methodologies to illustrate the contributions of these "classic" model biobanks to these research studies. Assessment of the three example articles supported by biobanks demonstrates that the output can have impact that is comparable to the impact of a set of benchmark articles describing milestones in the field of cancer research and cancer care. These case studies illustrate the value of the sustained investment of funds, planning, time, and effort on the part of the biobanks before the conduct of the research study to be able to ultimately support high-value research. The "value" model will enable further discussion around impact and may be useful in better delineating qualitative metrics of biobank value in the future.
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http://dx.doi.org/10.1089/bio.2021.0002DOI Listing
June 2021

Computational biomechanical modelling of the rabbit cranium during mastication.

Sci Rep 2021 Jun 23;11(1):13196. Epub 2021 Jun 23.

Aberdeen Centre for Arthritis and Musculoskeletal Health, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD, UK.

Although a functional relationship between bone structure and mastication has been shown in some regions of the rabbit skull, the biomechanics of the whole cranium during mastication have yet to be fully explored. In terms of cranial biomechanics, the rabbit is a particularly interesting species due to its uniquely fenestrated rostrum, the mechanical function of which is debated. In addition, the rabbit processes food through incisor and molar biting within a single bite cycle, and the potential influence of these bite modes on skull biomechanics remains unknown. This study combined the in silico methods of multi-body dynamics and finite element analysis to compute musculoskeletal forces associated with a range of incisor and molar biting, and to predict the associated strains. The results show that the majority of the cranium, including the fenestrated rostrum, transmits masticatory strains. The peak strains generated over all bites were found to be attributed to both incisor and molar biting. This could be a consequence of a skull shape adapted to promote an even strain distribution for a combination of infrequent incisor bites and cyclic molar bites. However, some regions, such as the supraorbital process, experienced low peak strain for all masticatory loads considered, suggesting such regions are not designed to resist masticatory forces.
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http://dx.doi.org/10.1038/s41598-021-92558-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222361PMC
June 2021

The effect of ambient sounds on decision-making and heart rate variability in autism.

Autism 2021 Jun 16:13623613211014993. Epub 2021 Jun 16.

University of Cambridge, UK.

Lay Abstract: Many autistic people report difficulties making decisions during everyday tasks, such as shopping. To examine the effect of sounds on decision-making, we developed a supermarket task where people watched a film shown from the shopper's perspective and were asked to make decisions between different products. The task was divided into three sections and participants completed each section in a different auditory environment: (1) no sounds, (2) non-social sounds (e.g. fridges humming) and (3) social sounds (e.g. people talking). Thirty-eight autistic and 37 neurotypical adults took part. We measured decision-making by examining how long it took to make a decision and how consistent people were with their decisions. We also measured heart rate variability because this biological response provides a measure of anxiety. After the supermarket shopping task, participants told us in their own words about their experiences. Autistic participants said that they found the non-social and social sound conditions more difficult than the no sound condition, and autistic participants found the social sound condition more negative than neurotypical participants. However, decision-making and heart rate variability were similar for autistic and neurotypical participants across the sound conditions, suggesting that these measures may not have been sensitive enough to reflect the experiences the autistic participants reported. Further research should consider alternative measures to explore the experiences reported by autistic people to help us understand which specific aspects of the environment autistic people are sensitive to. This, in turn, may enable more specific and evidence-based autism-friendly changes to be made.
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http://dx.doi.org/10.1177/13623613211014993DOI Listing
June 2021

The early course and treatment of posttraumatic stress disorder in very young children: diagnostic prevalence and predictors in hospital-attending children and a randomized controlled proof-of-concept trial of trauma-focused cognitive therapy, for 3- to 8-year-olds.

J Child Psychol Psychiatry 2021 Jun 14. Epub 2021 Jun 14.

Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.

Background: The introduction of developmentally adapted criteria for posttraumatic stress disorder (PTSD) has improved the identification of ≤6-year-old children with clinical needs. Across two studies, we assess predictors of the development of PTSD in young children (PTSD-YC), including the adult-led acute stress disorder (ASD) diagnosis, and provide proof of principle for cognitive-focused therapy for this age range, with the aim of increasing treatment options for children diagnosed with PTSD-YC.

Method: Study 1 (N = 105) assessed ASD and PTSD-YC diagnosis in 3- to 8-year-old children within one month and at around three months following attendance at an emergency room. Study 2 (N = 37) was a preregistered (www.isrctn.com/ISRCTN35018680) randomized controlled early-phase trial comparing CBT-3M, a cognitive-focused intervention, to treatment-as-usual (TAU) delivered within the UK NHS to 3- to 8-year-olds diagnosed with PTSD-YC.

Results: In Study 1, the ASD diagnosis failed to identify any young children. In contrast, prevalence of acute PTSD-YC (minus the duration requirement) was 8.6% in the first month post-trauma and 10.1% at 3 months. Length of hospital stay, but no other demographic or trauma-related characteristics, predicted development of later PTSD-YC. Early (within one month) diagnosis of acute PTSD-YC had a positive predictive value of 50% for later PTSD-YC. In Study 2, most children lost their PTSD-YC diagnosis following completion of CBT-3M (84.6%) relative to TAU (6.7%) and CBT-3M was acceptable to recipient families. Effect sizes were also in favor of CBT-3M for secondary outcome measures.

Conclusions: The ASD diagnosis is not fit for purpose in this age-group. There was a strong and encouraging signal of putative efficacy for young children treated using a cognitive-focused treatment for PTSD, and a larger trial of CBT-3M is now warranted.
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http://dx.doi.org/10.1111/jcpp.13460DOI Listing
June 2021

Regional patterning in tail vertebral form and function in chameleons (C. calyptratus).

Integr Comp Biol 2021 Jun 10. Epub 2021 Jun 10.

Evolutionary Morphology of Vertebrates, Ghent University, Belgium.

Previous studies have focused on documenting shape variation in the caudal vertebrae in chameleons underlying prehensile tail function. The goal of this study was to test the impact of this variation on tail function using multibody dynamic analysis (MDA). First, observations from dissections and 3D reconstructions generated from contrast-enhanced µCT-scans were used to document regional variation in arrangement of the caudal muscles along the antero-posterior axis. Using MDA, we then tested the effect of vertebral shape geometry on biomechanical function. To address this question, four different MDA models were built: those with a distal vertebral shape and with either a distal or proximal musculature, and reciprocally the proximal vertebral shape with either the proximal or distal musculature. For each muscle configuration, we calculated the force required in each muscle group for the muscle force to balance an arbitrary external force applied to the model. The results showed that the models with a distal-type of musculature are the most efficient, regardless of vertebral shape. Our models also showed that the m. ilio-caudalis pars dorsalis is least efficient when combining the proximal vertebral shape and distal musculature, highlighting the importance of the length of the transverse process in combination with the lever-moment arm onto which muscle force is exerted. This initial model inevitably has a number of simplifications and assumptions, however its purpose is not to predict in vivo forces, but instead reveals the importance of vertebral shape and muscular arrangement on the total force the tail can generate, thus providing a better understanding of the biomechanical significance of the regional variations on tail grasping performance in chameleons.
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http://dx.doi.org/10.1093/icb/icab125DOI Listing
June 2021

Towards an Understanding of Halide Interactions with the Carbonyl-Containing Molecule CH CHO.

Chemphyschem 2021 07 10;22(13):1316-1320. Epub 2021 Jun 10.

School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, 6009, Australia.

The anion photoelectron spectra of Cl ⋅⋅⋅CD CDO, Cl ⋅⋅⋅(CD CDO) , Br ⋅⋅⋅CH CHO, and I ⋅⋅⋅CH CHO are presented with electron stabilisation energies of 0.55, 0.93, 0.48, and 0.40 eV, respectively. Optimised geometries of the singly solvated species featured the halide appended to the CH CHO molecule in-line with the electropositive portion of the C=O bond and having binding energies between 45 and 52 kJ mol . The doubly solvated Cl ⋅⋅⋅(CH CHO) species features asymmetric solvation upon the addition of a second CH CHO molecule. Theoretical detachment energies were found to be in excellent agreement with experiment, with comparisons drawn between other halide complexes with simple carbonyl molecules.
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http://dx.doi.org/10.1002/cphc.202100180DOI Listing
July 2021

Value of Discharging Heart Failure Patients Home.

Authors:
Peter Y Watson

JAMA Cardiol 2021 Jun;6(6):725

Department of Health Care Management, Health Alliance Plan, Henry Ford Health System, Detroit, Michigan.

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http://dx.doi.org/10.1001/jamacardio.2021.0318DOI Listing
June 2021

Spectroscopic Investigation of Chalcogen Bonding: Halide-Carbon Disulfide Complexes.

Chemphyschem 2021 05 7;22(9):808-812. Epub 2021 Apr 7.

School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, 6009, Perth, Western Australia.

A combined experimental and theoretical approach has been used to study intermolecular chalcogen bonding. Specifically, the chalcogen bonding occurring between halide anions and CS molecules has been investigated using both anion photoelectron spectroscopy and high-level CCSD(T) calculations. The relative strength of the chalcogen bond has been determined computationally using the complex dissociation energies as well as experimentally using the electron stabilisation energies. The anion complexes featured dissociation energies on the order of 47 kJ/mol to 37 kJ/mol, decreasing with increasing halide size. Additionally, the corresponding neutral complexes have been examined computationally, and show three loosely-bound structural motifs and a molecular radical.
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http://dx.doi.org/10.1002/cphc.202100148DOI Listing
May 2021

A randomized, controlled proof-of-concept trial evaluating durable effects of memory flexibility training (MemFlex) on autobiographical memory distortions and on relapse of recurrent major depressive disorder over 12 months.

Behav Res Ther 2021 05 3;140:103835. Epub 2021 Mar 3.

Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, UK.

Low-intensity psychological interventions that target cognitive risk factors for depressive relapse may improve access to relapse prevention programs and thereby reduce subsequent risk. This study provides the first evaluation of an autobiographical memory-based intervention for relapse prevention, to establish whether memory-training programs that are efficacious for acute depression may also aid those currently in remission. We also provide the longest follow-up to-date of the effects of autobiographical memory training on autobiographical memory processes themselves. This pre-registered randomized-controlled proof-of-concept trial (N = 74) compared an autobiographical Memory Flexibility (MemFlex) intervention to Psychoeducation about cognitive-behavioral mechanisms which maintain depression. Both interventions were primarily self-guided, and delivered via paper workbooks completed over four weeks. The key cognitive outcome was ability to retrieve and alternate between specific and general autobiographical memories. Co-primary clinical outcomes were time until depressive relapse and depression-free days in the twelve-months following intervention. Results indicated a small-moderate effect size (d = 0.35) in favor of MemFlex for the cognitive outcome. A small Hazard Ratio (1.08) was observed for time until depressive relapse, along with a negligible effect size for depression-free days (d = 0.11). Although MemFlex produced long-term improvement in memory retrieval skills, there was little support for MemFlex as a relapse prevention program for depression.
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http://dx.doi.org/10.1016/j.brat.2021.103835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047774PMC
May 2021

Population Prevalence of the Posttraumatic Stress Disorder Subtype for Young Children in Nationwide Surveys of the British General Population and of Children in Care.

J Am Acad Child Adolesc Psychiatry 2021 Mar 2. Epub 2021 Mar 2.

Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom. Electronic address:

Objective: Posttraumatic stress disorder (PTSD) is a debilitating condition that when left untreated can have severe lifelong consequences for psychological, social, and occupational functioning. Initial conceptualizations of PTSD were centered on adult presentations. However, the instantiation of developmentally appropriate PTSD in young children (PTSD-YC) criteria, tailored to preschool (6 years old and younger) children, represents an important step toward identifying more young children experiencing distress. This study explored population-level prevalence of PTSD-YC indexed via an alternative algorithm for DSM-IV PTSD (AA-PTSD).

Method: Representative population data were used to test whether application of AA-PTSD criteria, relative to the DSM-IV PTSD algorithm, increased identification of 5- to 6-year-old children with clinical needs in both the general population (n = 3,202) and among looked after children (ie, children in care) (n = 137), in whom the risk of mental health issues is greater.

Results: Notably, no 5- to 6-year-old children in the general population sample were diagnosed with PTSD using adult-based DSM-IV criteria. In contrast, AA-PTSD prevalence was 0.4% overall, rising to 5.4% in trauma-exposed children. In looked after children, overall PTSD prevalence rose from 1.2% when applying adult-based DSM-IV criteria to 14% when using AA-PTSD criteria. Of trauma-exposed looked after children, 2.7% met criteria for DSM-IV PTSD compared with 57.0% when applying AA-PTSD criteria. In both samples, use of the alternative algorithm to index PTSD-YC criteria markedly increased identification of children experiencing functional impairment owing to symptoms.

Conclusion: Results demonstrate the utility of the PTSD-YC diagnosis beyond at-risk and treatment-seeking samples. Use of PTSD-YC criteria substantially improves identification of 5- to 6-year-old children burdened by PTSD at the population level.
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http://dx.doi.org/10.1016/j.jaac.2020.12.036DOI Listing
March 2021

1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer.

Sci Adv 2021 Jan 20;7(4). Epub 2021 Jan 20.

Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide -methyltransferase, the enzyme that catalyzes the transfer of a methyl group from -adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.
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http://dx.doi.org/10.1126/sciadv.abe1174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817098PMC
January 2021

Comparative cranial biomechanics in two lizard species: impact of variation in cranial design.

J Exp Biol 2021 03 11;224(Pt 5). Epub 2021 Mar 11.

Department of Engineering, Medical and Biological Engineering Research Group, University of Hull, Hull, HU6 7RX, UK.

Cranial morphology in lepidosaurs is highly disparate and characterised by the frequent loss or reduction of bony elements. In varanids and geckos, the loss of the postorbital bar is associated with changes in skull shape, but the mechanical principles underlying this variation remain poorly understood. Here, we sought to determine how the overall cranial architecture and the presence of the postorbital bar relate to the loading and deformation of the cranial bones during biting in lepidosaurs. Using computer-based simulation techniques, we compared cranial biomechanics in the varanid and the teiid , two large, active foragers. The overall strain magnitude and distribution across the cranium were similar in the two species, despite lower strain gradients in In , the postorbital bar is important for resistance of the cranium to feeding loads. The postorbital ligament, which in varanids partially replaces the postorbital bar, does not affect bone strain. Our results suggest that the reduction of the postorbital bar impaired neither biting performance nor the structural resistance of the cranium to feeding loads in Differences in bone strain between the two species might reflect demands imposed by feeding and non-feeding functions on cranial shape. Beyond variation in cranial bone strain related to species-specific morphological differences, our results reveal that similar mechanical behaviour is shared by lizards with distinct cranial shapes. Contrary to the situation in mammals, the morphology of the circumorbital region, calvaria and palate appears to be important for withstanding high feeding loads in these lizards.
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http://dx.doi.org/10.1242/jeb.234831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970069PMC
March 2021

A Permission to Contact Platform Is an Efficient and Cost-Effective Enrollment Method for a Biobank to Create Study-Specific Research Cohorts.

Biopreserv Biobank 2021 Jan 18. Epub 2021 Jan 18.

Biobanking and Biospecimen Research Services, Deeley Research Centre, BC Cancer, Victoria, Canada.

The permission to contact (PTC) platform is a useful mechanism to increase patient engagement and enrollment into biobanks. It provides biobanks with the ability to select specific patient cohorts and to complete consent to facilitate access to biospecimens and data. In this study, we evaluated consenting costs for a biobank to compile a research cohort based on utilizing a PTC platform to obtain consent as compared with utilizing a prospective consenting approach. In this study, we utilized a PTC platform to conduct an initial selection of potential participants for two breast cancer cohorts and to provide a "referral" to the biobank to recontact these patients to provide consent to access clinical archival biospecimens and associated data. We evaluated the effort, costs, and cohorts compiled by this approach to compare this mechanism with the alternative: compiling the same type of cohorts based on a classic biobank enrollment approach. After initial diagnosis and provision of a PTC up to 12 years before, recontact was possible in 84 of 90 (74%) and 77 of 107 (72%) breast cancer patients for preinvasive (ductal carcinoma [DCIS]) and invasive (triple-negative subtype) cancers. Of those recontacted, consent was completed in 42 of 84 (55%) DCIS patients and 48 of 107 (45%) triple negative breast cancer (TNBC) patients. The total cost of using PTC to recontact patients to compile these two consented cohorts was CAD $26.34 and CAD $20.11 per patient consent, respectively. We have demonstrated the feasibility of utilizing a PTC platform to obtain informed consent from patients for a specific study through referrals provided several years after initial PTC was provided. Depending on the existing biobank operational model and the efficiency of its processes for enrollment and obtaining broad informed consent, the implementation of a PTC platform may be an efficient and cost-effective complementary method for a biobank to enroll patients to develop criteria-specific cohorts to support research.
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http://dx.doi.org/10.1089/bio.2020.0114DOI Listing
January 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

Biobanking for Cancer Biomarker Research: Issues and Solutions.

Biomark Insights 2020 19;15:1177271920965522. Epub 2020 Oct 19.

Office of Biobank Education and Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Biomarkers are critical tools that underpin precision medicine. However there has been slow progress and frequent failure of biomarker development. The root causes are multifactorial. Here, we focus on the need for fast, efficient, and reliable access to quality biospecimens as a critical area that impacts biomarker development. We discuss the past history of biobanking and the evolution of biobanking processes relevant to the specific area of cancer biomarker development as an example, and describe some solutions that can improve this area, thus potentially accelerating biomarker research.
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http://dx.doi.org/10.1177/1177271920965522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594219PMC
October 2020

Photoelectron Spectroscopy and Structures of X ⋅⋅⋅CH O (X=F, Cl, Br, I) Complexes.

Chemphyschem 2021 Jan 1;22(1):69-75. Epub 2020 Dec 1.

School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, 6009, Australia.

A combined experimental and theoretical approach has been used to investigate X ⋅⋅⋅CH O (X=F, Cl, Br, I) complexes in the gas phase. Photoelectron spectroscopy, in tandem with time-of-flight mass spectrometry, has been used to determine electron binding energies for the Cl ⋅⋅⋅CH O, Br ⋅⋅⋅CH O, and I ⋅⋅⋅CH O species. Additionally, high-level CCSD(T) calculations found a C minimum for these three anion complexes, with predicted electron detachment energies in excellent agreement with the experimental photoelectron spectra. F ⋅⋅⋅CH O was also studied theoretically, with a C hydrogen-bonded complex found to be the global minimum. Calculations extended to neutral X⋅⋅⋅CH O complexes, with the results of potential interest to atmospheric CH O chemistry.
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http://dx.doi.org/10.1002/cphc.202000852DOI Listing
January 2021

Mood, Activity Participation, and Leisure Engagement Satisfaction (MAPLES): a randomised controlled pilot feasibility trial for low mood in acquired brain injury.

Pilot Feasibility Stud 2020 22;6:135. Epub 2020 Sep 22.

MRC Cognition and Brain Sciences Unit, University of Cambridge, 15 Chaucer Road, Cambridge, CB2 7EF UK.

Background: Acquired brain injury (ABI) affects approximately 79.3 million individuals annually and is linked with elevated rates of depression and low mood. Existing methods for treating depression in ABI have shown mixed efficacy. Behavioural activation (BA) is a potentially promising intervention. Its premise is that individuals with low mood avoid planning and engaging in activities due to low expectations of a positive outcome. Consequently, their exposure to positive reinforcement is reduced, exacerbating low mood. BA aims to break this cycle by encouraging activity planning and engagement. It is unknown whether cognitive demands of traditional BA may undermine efficacy in ABI. Here, we assess the feasibility and acceptability of two groups designed to increase activity engagement. In the activity planning group (traditional BA), the importance of meaningful and positive activity will be discussed and participants encouraged to plan/engage in activities in everyday life. The activity engagement group (experiential BA) instead focuses on engagement in positive experiences (crafts, games, discussion) the group. The primary aims are to evaluate the feasibility and acceptability of the two groups in ABI. A secondary aim is to explore relative efficacy of the groups compared to an equivalent period of waitlist controls.

Method: This study outlines a parallel-arm pilot feasibility trial for individuals with low mood and ABI that compares a traditional vs experiential BA group vs waitlist controls. Adults (≥ 18 years) will be recruited from local ABI services and randomised to condition. Feasibility and acceptability will be assessed via recruitment, retention, attendance and participant feedback. Groups will be compared (pre- and post-intervention and 1 month follow-up) by assessing self-reported activity engagement. Secondary outcomes include self-report measures of depression, anxiety, post-traumatic distress related to the ABI, motivation, participation and sense of control over one's life.

Ethics And Dissemination: The trial has been approved by the Health Research Authority of the NHS in the UK (East of England-Cambridge Central, REF 18/EE/0305). Results will inform future research on interventions for mood in ABI and be disseminated broadly via peer-reviewed journals, conference presentations and social media.

Trial Registration: ClinicalTrials.gov, NCT03874650 pre-results. Protocol version 2.1, March 5, 2019.
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http://dx.doi.org/10.1186/s40814-020-00660-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507282PMC
September 2020

The scale-dependent effectiveness of wildlife management: A case study on British deer.

J Environ Manage 2020 Dec 15;276:111303. Epub 2020 Sep 15.

Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Graham Kerr Building, Glasgow, G12 8QQ, UK; British Deer Society, The Walled Garden, Burgate Manor, Fordingbridge, Hants, SP6 1EF, UK. Electronic address:

Impacts of herbivory by wild ungulates represent a significant issue world-wide. To be effective, management of populations and impacts needs to be coordinated above the site scale, yet little research has investigated the appropriate spatial scale over which management should be integrated to be fully effective. In consideration of reduction of impacts in deciduous or mixed woodland habitats, we tested scale-specific management effectiveness in a lowland area of UK where moderate- to high-density populations of four deer species were the target of deliberate control programmes, and nonhuman predators were absent. We modelled the annual impact recorded between 2009 and 2015 in 98 woodlands as a function of cumulative culls of deer taken since the commencement of management. Analysis was repeated at different spatial scales by increasing the circular area around each focal woodland, from 2.5 km-radius up to 100 km-radius. Our findings suggest for the first time the geographical scale over which deer management needs to be coordinated for optimum effectiveness in decreasing their impact on woodland across relatively homogenous landscapes. For small bodied and relatively sedentary species (roe deer Capreolus capreolus; Reeves' muntjac Muntiacus reevesi), reductions in impacts within woodlands can be achieved by culling at the immediately local level, but some modest increase in effectiveness (probably relating to reductions in the degree of source-sink movement) may be expected with an increase in spatial scale of culling to around 30-70 km-radius. For larger-bodied, herding species with more extensive home-ranges (fallow deer Dama dama; red deer Cervus elaphus) management for reduction of woodland impacts was only really effective when coordinated above the single woodland-scale, with marked increases shown again up to a scale of 100 km-radius. Whilst future studies for different landscape types are still needed, our work emphasises that the spatial scale at which control plans are conducted can determine the effectiveness of wildlife management, possibly providing an advance on how to manage wildlife populations more effectively.
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http://dx.doi.org/10.1016/j.jenvman.2020.111303DOI Listing
December 2020

Improving Academic Biobank Value and Sustainability Through an Outputs Focus.

Value Health 2020 08 2;23(8):1072-1078. Epub 2020 Aug 2.

NSW Health Statewide Biobank, NSW Health Pathology, Professor Marie Bashir Centre, Camperdown, NSW, Australia. Electronic address:

Although it is generally accepted that human tissue biobanks are important to facilitate progress in health and medical research, many academic biobanks face sustainability challenges. We propose that biobank sustainability is challenged by a lack of available data describing the outputs and benefits that are produced by biobanks, as reflected by a dearth of publications that enumerate biobank outputs. We further propose that boosting the available information on biobank outputs and using a broader range of output metrics will permit economic analyses such as cost-consequence analyses of biobank activity. Output metrics and cost-consequence analyses can allow biobanks to achieve efficiencies, and improve the quality and/or quantity of their outputs. In turn, biobank output measures provide all stakeholders with explicit and accountable data on biobank value, which could contribute to the evolution of biobank operations to best match research needs, and mitigate some threats to biobank sustainability.
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http://dx.doi.org/10.1016/j.jval.2020.05.010DOI Listing
August 2020

Clinical Implication of Dosimetry Formalisms for Electronic Low-Energy Photon Intraoperative Radiation Therapy.

Pract Radiat Oncol 2021 Jan-Feb;11(1):e114-e121. Epub 2020 Aug 11.

Medical Physics Unit, McGill University, Montreal, QC, Canada.

Purpose: Intraoperative radiation therapy (IORT) using the INTRABEAM, a miniature x-ray source, has shown to be effective in treating breast cancer. However, recent investigations have suggested a significant deviation between the reported and delivered doses. In this work, the dose delivered by INTRABEAM in the TARGIT breast protocol was investigated, along with the dose from the Xoft Axxent, another source used in breast IORT.

Methods And Materials: The absorbed dose from the INTRABEAM was determined from ionization chamber measurements using: (a) the manufacturer-recommended formula (Zeiss V4.0 method), (b) a Monte Carlo calculated chamber conversion factor (C method), and (c) the formula consistent with the TARGIT breast protocol (TARGIT method). The dose from the Xoft Axxent was determined from ionization chamber measurements using the Zeiss V4.0 method and calculated using the American Association of Physicists in Medicine TG-43 formalism.

Results: For a nominal TARGIT prescription of 20 Gy, the dose at the INTRABEAM applicator surface ranged from 25.2 to 31.7 Gy according to the C method for the largest (5 cm) and smallest (1.5 cm) diameter applicator, respectively. The Zeiss V4.0 method results were 7% to 10% lower (23.2 to 28.6 Gy). At 1 cm depth, the C and Zeiss V4.0 absorbed doses were also larger than those predicted by the TARGIT method. The dose at 1 cm depth from the Xoft Axxent for a surface dose of 20 Gy was slightly less than INTRABEAM (3%-7% compared with C method). An exception was for the 3 cm applicator, where the Xoft dose was appreciably lower (31%).

Conclusions: The doses delivered in the TARGIT breast protocol with INTRABEAM were significantly greater than the prescribed 20 Gy and depended on the size of spherical applicator used. Breast IORT treatments with the Xoft Axxent received less dose compared with TARGIT INTRABEAM, which could have implications for studies comparing clinical outcomes between the 2 devices.
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http://dx.doi.org/10.1016/j.prro.2020.07.005DOI Listing
August 2020

The psychometric properties of the cognitive emotion regulation questionnaire (CERQ) in a clinical sample of adults with recurrent depression.

J Affect Disord 2020 11 15;276:212-219. Epub 2020 Jul 15.

University of Cambridge, Department of Psychology, Cambridge, United Kingdom; School of Psychology, University of New South Wales, Sydney, Australia.

Background: Affective dysregulation is central to depression. However, emotion regulation (ER) tendencies in depression remain poorly understood. It is critical, therefore, to validate measures of habitual ER in clinical populations. The current study aimed to validate the Cognitive Emotion Regulation Questionnaire (CERQ) in a sample of individuals with a history of recurrent depression who are currently in remission.

Method: The CERQ measures ER tendencies with 36 self-report items that are divided into nine subscales. Each subscale is purported to assess one of five adaptive and four maladaptive ER strategies. The CERQ was administered to 476 adults (mean age = 46.76 years; 75% female) that were currently in remission with a history of recurrent depression, who were recruited from primary care settings. We first investigated the CERQ's nine factor structure, internal consistency, convergent and criterion validity.

Results: The nine-factor structure did not fit the CERQ structure in a sample of individuals with recurrent depression and convergent validity was poor. Instead, a five-factor structure fit the data best and showed acceptable convergent and criterion validity.

Limitations: The generalisability of the findings may be limited due to relative lack of diversity in terms of gender and ethnicity of the sample.

Conclusion: These results suggest that the taxonomic structure of the CERQ does not fit emotion regulation patterns in adults with a history of depression. These findings highlight the importance of validating measures in clinical samples.
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http://dx.doi.org/10.1016/j.jad.2020.06.061DOI Listing
November 2020

Long-term cognitive outcome in adult survivors of an early childhood posterior fossa brain tumour.

Int J Clin Oncol 2020 Oct 8;25(10):1763-1773. Epub 2020 Jul 8.

Cambridgeshire and Peterborough NHS Foundation Trust, South Team, Comberton Road, Toft, Cambridgeshire, CB23 2RY, UK.

Purpose: Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT.

Methods: 62 adult survivors of a PFT, ascertained from a national register, diagnosed before 5 years of age, and a sibling control, received a single IQ assessment an average of 32 years (range 18-53) after initial diagnosis, using the Weschler Abbreviated Scale of Intelligence. Regression models were fitted to survivor-sibling pair differences on verbal and performance IQ (VIQ and PIQ) scores to investigate whether increasing time between PFT diagnosis and follow-up IQ assessment contributed to survivor-sibling IQ differences.

Results: At follow-up, survivors had, on average, VIQ 15 points and PIQ 19 points lower than their siblings. There was no significant effect of time since diagnosis on survivor-sibling VIQ difference. Survivors who received radiotherapy showed no significant effect of time since diagnosis on survivor-sibling PIQ difference. Survivors who did not receive radiotherapy demonstrated a trend for it to reduce.

Conclusions: VIQ and PIQ deficits persist in adulthood, suggesting the effect of a fixed injury imposing on cognitive development, rather than an ongoing pathological process.

Implications For Cancer Survivors: The findings will help parents and others supporting survivors of an early life PFT to identify and plan for possible cognitive outcomes, and highlight the importance of early interventions to optimize cognitive function during the developmental period.
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http://dx.doi.org/10.1007/s10147-020-01725-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498491PMC
October 2020

The influence of musculoskeletal forces on the growth of the prenatal cortex in the ilium: a finite element study.

Comput Methods Biomech Biomed Engin 2020 Oct 13;23(13):959-967. Epub 2020 Jun 13.

Medical and Biological Engineering Research Group, Department of Engineering, University of Hull, Hull, UK.

Remodelling and adaptation of bone within the pelvis is believed to be influenced by the mechanical strains generated during locomotion. Variation in the cortical bone thickness observed in the prenatal ilium has been linked to the musculoskeletal loading associated with movements; for example the development of a thicker gluteal cortex is a possible response to contractions of the gluteal muscles. This study examines if the strains generated in the prenatal iliac cortex due to musculoskeletal loading are capable of initiating bone remodelling to either maintain homeostasis or form new bone. Computational modelling techniques were used firstly to predict the muscle forces and resultant joint reaction force acting on the pelvis during a range of movements. Finite element analyses were subsequently performed to calculate the von Mises strains induced in the prenatal ilium. The results demonstrated that strains generated in the iliac cortex were above the thresholds suggested to regulate bone remodelling to either maintain homeostasis or form new bone. Further simulations are required to investigate the extent to which the heterogeneous cortex forms in response to these strains (i.e., remodelling) or if developmental bone modelling plays a more pivotal role.
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http://dx.doi.org/10.1080/10255842.2020.1777546DOI Listing
October 2020

Taking care of our future doctors: a service evaluation of a medical student mental health service.

BMC Med Educ 2020 May 29;20(1):172. Epub 2020 May 29.

School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Background: Studies suggest medical students experience high levels of mental distress during training but are less likely, than other students, to access care due to stigma and concerns regarding career progression. In response, The School of Clinical Medicine, University of Cambridge supported the development of the 'Clinical Student Mental Health Service' to provide specialist input for this vulnerable group. This study evaluates the efficiency and effectiveness of this service.

Methods: Using mixed-methods, cross-sectional analysis of validated psychiatric rating scales and qualitative feedback, 89 responses were analysed from 143 clinical students referred, between 2015 and 2019. The care pathway included initial review by a psychiatrist, who triaged students to psychologists delivering therapies including: Cognitive Behavioural Therapy, Interpersonal Therapy, Eye Movement Desensitization Reprocessing Therapy or Cognitive Analytic Therapy. Efficiency was assessed by waiting times for psychiatry and psychology interventions, and number of sessions. Academic outcomes included school intermission and graduation. Clinical effectiveness was analysed by measuring global distress, depression, anxiety, functioning and suicidal risk. Pre/post intervention changes were captured using t-test and McNemar test with thematic analysis of qualitative feedback.

Results: Referral rates increased from 3.93% (22/560) in 2015 to 6.74% (45/668) in 2018. Median waiting times for initial psychiatric assessment and start of therapy was 26 and 33 days, respectively. All graduating students moved on to work as junior doctors. Levels of distress, (t = 7.73, p < 0.001, df = 31), depression (t = 7.26, p < 0.001, df = 34) anxiety (Z = - 4.63, p < 0.001) and suicide risk (Z = - 3.89, p < 0.001) were significantly reduced. Participant's functioning was significantly improved (p < 0.001, 99.5% CI 4.55 to 14.62). Feedback indicated high satisfaction with the rapid access and flexibility of the service and the team clinicians.

Conclusions: A significant proportion of medical students attending the service scored highly on validated rating scales measuring emotional distress, suicidality and mental illness. Reassuringly they benefitted from timely specialist mental health input, showing improvements in mental well-being and improved functioning. The development and design of this service might serve as an exemplar for medical schools developing similar support for their students.
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http://dx.doi.org/10.1186/s12909-020-02075-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257172PMC
May 2020

Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma.

J Clin Oncol 2020 08 26;38(22):2519-2529. Epub 2020 May 26.

Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD.

Purpose: Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma.

Methods: We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS).

Results: Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare.

Conclusion: Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
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http://dx.doi.org/10.1200/JCO.20.00303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392744PMC
August 2020

Changes of the acute and chronic toxicity of three antimicrobial agents to Daphnia magna in the presence/absence of micro-polystyrene.

Environ Pollut 2020 Aug 9;263(Pt A):114551. Epub 2020 Apr 9.

Key Laboratory of New Membrane Materials, Ministry of Industry and Information Technology, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China. Electronic address:

The effects of microplastics on aquatic organisms are drawing growing attention, but little has been focused on their effects on the toxicity of other chemicals. In this study, we examined the acute and chronic toxicity of micro-polystyrene (5.8 μm dia.), and its effects on the toxicity of three antimicrobial agents (triclosan, triclocarban and methyl-triclosan) to Daphnia magna. Results indicated that polystyrene had a low acute toxicity with an EC of 36.5 mg/L. The presence of polystyrene (1 mg/L) did not produce significant effect on the acute toxicity of three chemicals, because the 95% confidence intervals of their EC values had a large overlap of 11.3%-48.3%. For the 21 day chronic toxicity, polystyrene alone had significant toxicity with concentrations of at least 2 mg/L, which prolonged the time of the first brood, limited the number of broods, and reduced the total number of neonates. Compared with the chemicals alone, the addition of polystyrene enhanced their reproduction toxicity. Based on the various reproduction indicators, an intrinsic rate of natural increase (r) was calculated to assess the rate of population growth. Results suggested that the r values of three chemicals decreased in the presence of PS, and further decreased with increasing PS concentrations. Among the three chemicals, methyl-triclosan was the most affected. These results suggested that the presence of microplastics would exacerbate the detrimental influence of pollutants on Daphnia magna.
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http://dx.doi.org/10.1016/j.envpol.2020.114551DOI Listing
August 2020

UBCx "Biospecimen Research Methods Course".

Biopreserv Biobank 2020 Feb;18(1):4-6

Biobanking and Biospecimen Research Services, Trev and Joyce Deeley Research Centre, BC Cancer, Victoria, Canada.

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http://dx.doi.org/10.1089/bio.2019.0046DOI Listing
February 2020

Imaginator: A Proof-of-Concept Feasibility Trial of a Brief Imagery-Based Psychological Intervention for Young People Who Self-Harm.

Suicide Life Threat Behav 2020 06 14;50(3):724-740. Epub 2020 Feb 14.

Department of Psychology, Uppsala University, Uppsala, Sweden.

Objectives: The Imaginator study tested the feasibility of a short mental imagery-based psychological intervention for young people who self-harm and used a stepped-wedge design to investigate effects on self-harm frequency reduction at 3 and 6 months.

Method: A total of 38 participants aged 16-25 were recruited via community self-referral and mental health services. Participants were randomized to immediate delivery of Functional Imagery Training (FIT) or usual care followed by delayed delivery after 3 months. FIT comprised two face-to-face sessions, five phone sessions, and use of a smartphone app. Outcomes' assessment was blind to allocation.

Results: Three quarters of those who began treatment completed face-to-face sessions, and 57% completed five or more sessions in total. Self-harm frequency data were obtained on 76% of the sample at 3 months (primary outcome) and 63% at 6 months. FIT produced moderate reductions in self-harm frequency at 3 months after immediate (d = 0.65) and delayed delivery (d = 0.75). The Immediate FIT group maintained improvements from 3 to 6 months (d = 0.05). Participants receiving usual care also reduced self-harm (d = 0.47).

Conclusions: A brief mental imagery-based psychological intervention targeting self-harm in young people is feasible and may comprise a novel transdiagnostic treatment for self-harm.
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http://dx.doi.org/10.1111/sltb.12620DOI Listing
June 2020
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