Publications by authors named "Emma Chapman"

31 Publications

Practice review: Evidence-based and effective management of fatigue in patients with advanced cancer.

Palliat Med 2021 Dec 14:2692163211046754. Epub 2021 Dec 14.

Academic Unit of Palliative Care, Leeds Institute of Health Sciences, Leeds, UK.

Background: Fatigue affects most patients living with advanced cancer and is a symptom that healthcare professionals can find difficult to manage.

Aim: To provide healthcare professionals with a pragmatic overview of approaches to management of fatigue in patients with advanced cancer that are commonly recommended by guidelines and to evaluate evidence underpinning them.

Design: Scoping review methodology was used to determine the strength of evidence supporting use of interventions recommended in management of fatigue in patients with advanced cancer.

Data Sources: National or international guidelines were examined if they described the management of fatigue in adult cancer patients and were written within the last 6 years (2015-2021) in English. The Cochrane Database of Systematic Reviews (January 2011-December 2021) was searched for 'cancer' AND 'fatigue' in title, abstract or keywords. A PubMed search was also made.

Results: Evidence indicates physical exercise interventions are effective and patients may benefit from energy conservation tactics. Evidence does not support use of psychostimulants such as methylphenidate. Limited data were found on efficacy of corticosteroids, psychological interventions, nutritional intervention, sleep optimization or complementary therapies for management of fatigue in advanced cancer.

Conclusion: We recommend regular assessment, review and acknowledgement of the impact of fatigue. Exercise and energy conservation should be considered. Pharmacological interventions are not endorsed as a routine approach. Many interventions currently recommended by guidelines are not supported by a robust evidence base and further research on their efficacy is required.
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http://dx.doi.org/10.1177/02692163211046754DOI Listing
December 2021

Tuning the Cloud-Point and Flocculation Temperature of Poly(2-(diethylamino)ethyl methacrylate)-Based Nanoparticles via a Postpolymerization Betainization Approach.

ACS Polym Au 2021 Aug 8;1(1):47-58. Epub 2021 Jul 8.

School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

The ability to tune the behavior of temperature-responsive polymers and self-assembled nanostructures has attracted significant interest in recent years, particularly in regard to their use in biotechnological applications. Herein, well-defined poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA)-based core-shell particles were prepared by RAFT-mediated emulsion polymerization, which displayed a lower-critical solution temperature (LCST) phase transition in aqueous media. The tertiary amine groups of PDEAEMA units were then utilized as functional handles to modify the core-forming block chemistry via a postpolymerization betainization approach for tuning both the cloud-point temperature ( ) and flocculation temperature ( ) of these particles. In particular, four different sulfonate salts were explored aiming to investigate the effect of the carbon chain length and the presence of hydroxyl functionalities alongside the carbon spacer on the particle's thermoresponsiveness. In all cases, it was possible to regulate both and of these nanoparticles upon varying the degree of betainization. Although was found to be dependent on the type of betainization reagent utilized, it only significantly increased for particles betainized using sodium 3-chloro-2-hydroxy-1-propanesulfonate, while varying the aliphatic chain length of the sulfobetaine only provided limited temperature variation. In comparison, the onset of flocculation for betainized particles varied over a much broader temperature range when varying the degree of betainization with no real correlation identified between and the sulfobetaine structure. Moreover, experimental results were shown to partially correlate to computational oligomer hydrophobicity calculations. Overall, the innovative postpolymerization betainization approach utilizing various sulfonate salts reported herein provides a straightforward methodology for modifying the thermoresponsive behavior of soft polymeric particles with potential applications in drug delivery, sensing, and oil/lubricant viscosity modification.
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http://dx.doi.org/10.1021/acspolymersau.1c00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389998PMC
August 2021

The Uptake of Sporopollenin Exine Capsules and Associated Bioavailability of Adsorbed Oestradiol in Selected Aquatic Invertebrates.

Bull Environ Contam Toxicol 2021 Nov 30;107(5):876-882. Epub 2021 Aug 30.

Department of Biological and Marine Sciences, University of Hull, Cottingham Rd, Hull, HU6 7RX, UK.

Lycopodium clavatum sporopollenin exine capsules (SpECs) are known to both adsorb and absorb chemicals. The aim of the present work was to determine whether oestradiol (E2) is 'bioavailable' to bioindicator species, either pre-adsorbed to, or in the presence of, SpECs. SpEC uptake was confirmed for Daphnia magna and Dreissena bugensis. E2 levels varied among treatments for Caenorhabditis elegans though there was no relationship to SpEC load. E2 was not detected in D. bugensis tissues. Expression changes of general stress and E2-specific genes were measured. For C. elegans, NHR-14 expression suggested that SpECs modulate E2 impacts, but not general health responses. For D. magna, SpECs alone and with E2 changed Vtg1 and general stress responses. For D. bugensis, SpECS were taken up but no E2 or change in gene expression was detected after exposure to E2 and/or SpECs. The present study is the first to investigate SpECs and bound chemical dynamics.
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http://dx.doi.org/10.1007/s00128-021-03364-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556174PMC
November 2021

Consequences of combined exposure to thermal stress and the plasticiser DEHP in Mytilus spp. differ by sex.

Mar Pollut Bull 2021 Sep 16;170:112624. Epub 2021 Jun 16.

Department of Biological and Marine Sciences, University of Hull, Hull HU6 7RX, United Kingdom. Electronic address:

Little is known about the combined effect of environmental factors and contaminants on commercially important marine species, and whether this effect differs by sex. In this study, blue mussels were exposed for seven days to both single and combined stressors (i.e., +3 °C elevated temperature and two environmentally relevant concentrations of the plastic softener DEHP, 0.5 and 50 μg/l) in a factorial design. Males were observed to be more sensitive to high temperature, demonstrated by the significant increase in out-of-season spawning gonads and higher gene expression of the antioxidant catalase and the estrogen receptor genes. On the other hand, while the gametogenesis cycle in females was more resilient than in males, DEHP exposure altered the estrogen-related receptor gene expression. We show that the combined stressors DEHP and increased temperature, in environmentally relevant magnitudes, have different consequences in male and female mussels, with the potential to impact the timing and breeding season success in Mytilus spp.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112624DOI Listing
September 2021

Understanding the role of hospice pharmacists: a qualitative study.

Int J Clin Pharm 2021 Dec 13;43(6):1546-1554. Epub 2021 Jun 13.

University of Leeds, Leeds, UK.

Background Pharmacists are important members of multidisciplinary teams but, despite surveys of provision, the role of the hospice pharmacist is not well described. Objective To explore the role of the hospice pharmacist and identify barriers and facilitators to the role. Setting Hospices offering in-patient services caring for adults towards the end of life in one geographical area of northern England. Method Pharmacists providing services to hospices were invited to take part in qualitative semi-structured interviews asking about experience, patient contact, team working and barriers and facilitators to the role. These were recorded verbatim and data were analysed thematically using framework analysis. Main outcome measure The hospice pharmacist's perceptions of their role and barriers and facilitators to it. Results Fifteen pharmacists took part. Two themes and ten subthemes were identified focused on tasks and communication. Practise was varied and time limited the quantity and depth of services carried out but was often spent navigating complex drug supply routes. Participants found methods of communication suited to the hours they spent in the hospice although communication of data was a barrier to effective clinical service provision. Participants identified the need for appropriate training and standards of practice for hospice pharmacists would enable better use of their skills. Conclusion Barriers to the role of hospice pharmacist include time, access to role specific training, access to clinical information and complex medicines supply chains. The role would benefit from definition to ensure that hospices are able to use hospice pharmacists to their greatest potential.
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http://dx.doi.org/10.1007/s11096-021-01281-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642336PMC
December 2021

A national survey of hospice pharmacists and a comparison with international models.

Int J Pharm Pract 2021 May;29(3):252-257

Academic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.

Background: Pharmacists can contribute to improved patient outcomes, improve medicine knowledge, reduce drug costs and minimise errors. However, their role within hospice-based services is not well described.

Objective: The objective of this paper was to explore the role of pharmacists within UK hospices.

Methods: Methods include an online survey and follow-up telephone contact of pharmacists working in UK hospices assessing pharmacist provision, duties, communication, medicine sourcing and training.

Results: Eighty-nine responses were received from 82 hospices (response rate 50%). Pharmacists had a role in 75% of hospices providing between 6.6 min and 5.5 hrs of pharmacist support per bed per week. The most frequent duty reported was provision of medicines information to the clinical team. Access to patient records varied considerably: 13% had full read and write access to GP records while 29% had no access. Job-specific training had not been received by 36% of the respondents and 47% reported training needs including basic training in palliative care.

Conclusions: Three-quarters of UK hospices have pharmacy provision, although this falls below the recommended levels in the majority. Hospice pharmacists lack access to training and records. Medicines sourcing for hospices is variable and could provide opportunities for efficiencies with further research.
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http://dx.doi.org/10.1093/ijpp/riab002DOI Listing
May 2021

Duration of palliative care before death in international routine practice: a systematic review and meta-analysis.

BMC Med 2020 11 26;18(1):368. Epub 2020 Nov 26.

Academic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.

Background: Early provision of palliative care, at least 3-4 months before death, can improve patient quality of life and reduce burdensome treatments and financial costs. However, there is wide variation in the duration of palliative care received before death reported across the research literature. This study aims to determine the duration of time from initiation of palliative care to death for adults receiving palliative care across the international literature.

Methods: We conducted a systematic review and meta-analysis that was registered with PROSPERO (CRD42018094718). Six databases were searched for articles published between Jan 1, 2013, and Dec 31, 2018: MEDLINE, Embase, CINAHL, Global Health, Web of Science and The Cochrane Library, as well undertaking citation list searches. Following PRISMA guidelines, articles were screened using inclusion (any study design reporting duration from initiation to death in adults palliative care services) and exclusion (paediatric/non-English language studies, trials influencing the timing of palliative care) criteria. Quality appraisal was completed using Hawker's criteria and the main outcome was the duration of palliative care (median/mean days from initiation to death).

Results: One hundred sixty-nine studies from 23 countries were included, involving 11,996,479 patients. Prior to death, the median duration from initiation of palliative care to death was 18.9 days (IQR 0.1), weighted by the number of participants. Significant differences between duration were found by disease type (15 days for cancer vs 6 days for non-cancer conditions), service type (19 days for specialist palliative care unit, 20 days for community/home care, and 6 days for general hospital ward) and development index of countries (18.91 days for very high development vs 34 days for all other levels of development). Forty-three per cent of studies were rated as 'good' quality. Limitations include a preponderance of data from high-income countries, with unclear implications for low- and middle-income countries.

Conclusions: Duration of palliative care is much shorter than the 3-4 months of input by a multidisciplinary team necessary in order for the full benefits of palliative care to be realised. Furthermore, the findings highlight inequity in access across patient, service and country characteristics. We welcome more consistent terminology and methodology in the assessment of duration of palliative care from all countries, alongside increased reporting from less-developed settings, to inform benchmarking, service evaluation and quality improvement.
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http://dx.doi.org/10.1186/s12916-020-01829-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690105PMC
November 2020

Identification of patients with potential palliative care needs: A systematic review of screening tools in primary care.

Palliat Med 2020 09 7;34(8):989-1005. Epub 2020 Jun 7.

Academic Unit of Palliative Care, Leeds Institute of Health Sciences (LIHS), School of Medicine, University of Leeds, Leeds, UK.

Background: Despite increasing evidence of the benefits of early access to palliative care, many patients do not receive palliative care in a timely manner. A systematic approach in primary care can facilitate earlier identification of patients with potential palliative care needs and prompt further assessment.

Aim: To identify existing screening tools for identification of patients with advanced progressive diseases who are likely to have palliative care needs in primary healthcare and evaluate their accuracy.

Design: Systematic review (PROSPERO registration number CRD42019111568).

Data Sources: Cochrane, MEDLINE, Embase and CINAHL were searched from inception to March 2019.

Results: From 4,127 unique articles screened, 25 reported the use or development of 10 screening tools. Most tools use prediction of death and/or deterioration as a proxy for the identification of people with potential palliative care needs. The tools are based on a wide range of general and disease-specific indicators. The accuracy of five tools was assessed in eight studies; these tools differed significantly in their ability to identify patients with potential palliative care needs with sensitivity ranging from 3% to 94% and specificity ranging from 26% to 99%.

Conclusion: The ability of current screening tools to identify patients with advanced progressive diseases who are likely to have palliative care needs in primary care is limited. Further research is needed to identify standardised screening processes that are based not only on predicting mortality and deterioration but also on anticipating the palliative care needs and predicting the rate and course of functional decline. This would prompt a comprehensive assessment to identify and meet their needs on time.
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http://dx.doi.org/10.1177/0269216320929552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388141PMC
September 2020

A preliminary analysis of microplastics in edible versus non-edible tissues from seafood samples.

Environ Pollut 2020 Aug 27;263(Pt A):114452. Epub 2020 Mar 27.

Department of Biological and Marine Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, United Kingdom. Electronic address:

Plastics have been widely reported to be present in the environment yet there are still many questions regarding the extent of this and the impacts these may have on both the environment and human health. The purpose of this investigation is to determine levels of micro and mesoplastic (MP), in the 1-5000 μm range, in commercially important species of finfish and shellfish. Additionally, to determine and compare the relative MP levels in edible versus non-edible tissues, and consider the wider implications in terms of human health concerns with a preliminary risk identification approach. For several fish species, samples taken from typically non-edible (gills, digestive system) and edible (muscle) flesh, and were analysed separately. Scallops, where all tissues are edible, were analysed whole. Significant differences were observed in the number of particles isolated from the finfish gills and digestive tissues relative to the control samples, but not in the edible flesh. For scallops, the abundance of particles in the Scottish samples did not vary significantly from the control, while the Patagonian scallops displayed significantly higher numbers of MPs. Characterisation of MPs by FTIR microscopy found that 16-60% (depending on species) were polyethylene terephthalate (PET) and polyethylene (PE) in origin. The risk identification results validate MPs as an emerging risk in the food chain and establish seafood as a vector for the exposure and uptake of MPs through the ingestion route for humans. Levels of MPs in seafood, and a direct link to the human food chain, suggests that their quantification be included as one food safety measure.
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http://dx.doi.org/10.1016/j.envpol.2020.114452DOI Listing
August 2020

Influence of light and temperature cycles on the expression of circadian clock genes in the mussel Mytilus edulis.

Mar Environ Res 2020 Jul 23;159:104960. Epub 2020 Mar 23.

Department of Biological and Marine Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, United Kingdom. Electronic address:

Clock genes and environmental cues regulate essential biological rhythms. The blue mussel, Mytilus edulis, is an ecologically and economically important intertidal bivalve undergoing seasonal reproductive rhythms. We previously identified seasonal expression differences in M. edulis clock genes. Herein, the effects of light/dark cycles, constant darkness, and daily temperature cycles on the circadian expression patterns of such genes are characterised. Clock genes Clk, Cry1, ROR/HR3, Per and Rev-erb/NR1D1, and Timeout-like, show significant mRNA expression variation, persisting in darkness indicating endogenous control. Rhythmic expression was apparent under diurnal temperature cycles in darkness for all except Rev-erb. Temperature cycles induced a significant expression difference in the non-circadian clock-associated gene aaNAT. Furthermore, Suppression Subtractive Hybridisation (SSH) was used to identify seasonal genes with potential links to molecular clock function and revealed numerous genes meriting further investigation. Understanding the relationship between environmental cues and molecular clocks is crucial in predicting the outcomes of environmental change on fundamental rhythmic processes.
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http://dx.doi.org/10.1016/j.marenvres.2020.104960DOI Listing
July 2020

Practice review: Evidence-based and effective management of pain in patients with advanced cancer.

Palliat Med 2020 04 24;34(4):444-453. Epub 2020 Jan 24.

Academic Unit of Palliative Care, Leeds Institute of Health Sciences, Leeds, UK.

Background: Pain of a moderate or severe intensity affects over half of patients with advanced cancer and remains undertreated in at least one-third of these patients.

Aim: The aim of this study was to provide a pragmatic overview of the evidence supporting the use of interventions in pain management in advanced cancer and to identify where encouraging preliminary results are demonstrated but further research is required.

Design: A scoping review approach was used to examine the evidence supporting the use of guideline-recommended interventions in pain management practice.

Data Sources: National or international guidelines were selected if they described pain management in adult cancer patients and were written within the last 5 years in English. The Cochrane Database of Systematic Reviews (January 2014 to January 2019) was searched for 'cancer' AND 'pain' in the title, abstract or keywords. A MEDLINE search was also made.

Results: A strong opioid remains the drug of choice for treating moderate or severe pain. Bisphosphonates and radiotherapy are also effective for cancer-related bone pain. Optimal management requires a tailored approach, support for self-management and review of treatment outcomes. There is likely a role for non-pharmacological approaches. Paracetamol should not be used in patients taking a strong opioid to treat pain. Cannabis-based medicines are not recommended. Weak opioids, ketamine and lidocaine are indicated in specific situations only.

Conclusion: Interventions commonly recommended by guidelines are not always supported by a robust evidence base. Research is required to evaluate the efficacy of non-steroidal anti-inflammatory drugs, anti-convulsants, anti-depressants, corticosteroids, some invasive anaesthetic techniques, complementary therapies and transcutaneous electrical nerve stimulation.
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http://dx.doi.org/10.1177/0269216319896955DOI Listing
April 2020

PVC Does Not Influence Cadmium Uptake or Effects in the Mussel (Mytilus edulis).

Bull Environ Contam Toxicol 2020 Mar 20;104(3):315-320. Epub 2020 Jan 20.

School of Environmental Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, UK.

Microplastics have become a global concern in recent years. In this study, we studied (i) whether the presence of polyvinyl chloride (PVC) microparticles may affect cadmium (Cd) uptake in mussel (Mytilus edulis); and (ii) the biological effects of PVC microparticles exposure alone or in combination with Cd. Significant Cd uptake in digestive gland was observed following Cd exposure. However, PVC did not significantly increase Cd uptake compared with Cd alone treatment. In terms of biological impacts, significantly lower neutral red retention (NRR) time and elevated expression of Metallothionein isoform 20-IV (MT-20) were observed in mussels exposed to Cd alone, or combined with microplastics, yet there was no significant difference between them. catalase (CAT) expression only showed a significant increase in mussels exposed to Cd alone. This work provides an insight into the relationship on resulting biological impacts between these two contaminants.
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http://dx.doi.org/10.1007/s00128-020-02789-xDOI Listing
March 2020

Making Power Visible: "Slow Activism" to Address Staff Sexual Misconduct in Higher Education.

Violence Against Women 2019 09;25(11):1309-1330

3 Imperial College London, UK.

This article examines activism to address staff-to-student sexual misconduct in higher education in the United Kingdom from our perspective as founders and members of the research and lobby organization The 1752 Group. We argue that in order to tackle staff sexual misconduct in higher education, the problem has first to be made visible. We theorize this as "slow activism" and outline the activities that we and others have been engaged in toward this end: conducting research, using complaints processes within institutions, naming the experiences of staff sexual misconduct and/or institutions and perpetrators, and carrying out discipline-led and sector-level initiatives.
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http://dx.doi.org/10.1177/1077801219844606DOI Listing
September 2019

Seasonal expression patterns of clock-associated genes in the blue mussel Mytilus edulis.

Chronobiol Int 2017 17;34(9):1300-1314. Epub 2017 Oct 17.

a School of Environmental Sciences , University of Hull , Hull , UK.

Environmental cues allow organisms to synchronise their internal biological rhythms with external environmental cycles. These rhythms are regulated on a molecular level by oscillating interactions between clock genes and their proteins. Light is a particularly relevant environmental cue, provisioning daily information via light/dark cycles as well as seasonal information via day-length (photoperiod). Despite the ecological and commercial importance of bivalves, little is known about the interactions comprising their molecular clock mechanism. This study investigates the link between the annual seasonal progression and reproductive development in the blue mussel (Mytilus edulis), using mRNA expression patterns of clock-associated genes: Clock, Cry1¸ ARNT, Timeout-like, ROR/HR3 and aaNAT, in the gonads of both sexes, sampled over three daily time-points on a tidal beach during the winter and summer solstices. Significant differences in mRNA expression levels, including some seasonal differences at comparable time-points, were detected for all genes with the exception of Timeout-like. These differences occurred seasonally within sex (Clock, Cry1, ROR/HR3), seasonally between sexes (Clock, Cry1, ARNT, ROR/HR3, aaNAT) and daily between sexes (Cry1), although no significant daily differences were detected in summer or winter for either sex for any of the genes. This study reveals that clock-associated genes show seasonal responses in this species of bivalve. Understanding the mechanisms by which environmental cues drive biological rhythms is critical to understanding the seasonal sensitivity of this keystone species to environmental changes.
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http://dx.doi.org/10.1080/07420528.2017.1363224DOI Listing
August 2018

Hepatocellular adenoma in a European flatfish (Limanda limanda): Genetic alterations in laser-capture micro-dissected tissue and global transcriptomic approach.

Mar Pollut Bull 2017 Jun 3;119(2):120-127. Epub 2017 May 3.

School of Environmental Sciences, University of Hull, Cottingham Road, Hull HU6 7RX, United Kingdom. Electronic address:

Liver tumours in flatfish have been diagnosed using histopathology for decades to monitor the impacts of marine pollution. Here we describe the application of specific gene (retinoblastoma, Rb) profiling in laser capture micro-dissected samples, and a suppression subtractive hybridization (SSH) approach to isolate differentially expressed genes in hepatocellular adenoma (HCA) samples from dab, Limanda limanda. The Rb profiles from apparently normal and HCA micro-dissected samples of fish from the North Sea showed no significant difference, and genotypic heterogeneity within defined histological phenotypes was observed. In the SSH, sequences associated with cell signalling, cell cycle, gene expression regulation, protein transport and protein degradation were isolated. These included up-regulation of arrestin domain containing 3 (arrdc3), Rac-1 and tribbles, and down-regulation of ankyrin repeat/sterile alpha-motif domain-containing protein 1B-like (ANKS1B-like), c-fos, CDKN1B and RhoA-like sequences, previously implicated in mammalian HCA. This study offers new candidates involved in fish liver tumour development.
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http://dx.doi.org/10.1016/j.marpolbul.2017.04.052DOI Listing
June 2017

Molecular changes in skin pigmented lesions of the coral trout Plectropomus leopardus.

Mar Environ Res 2016 Sep 28;120:130-5. Epub 2016 Jul 28.

School of Biological, Biomedical and Environmental Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, United Kingdom. Electronic address:

A high prevalence of skin pigmented lesions of 15% was recently reported in coral trout Plectropomus leopardus, a commercially important marine fish, inhabiting the Great Barrier Reef. Herein, fish were sampled at two offshore sites, characterised by high and low lesion prevalence. A transcriptomic approach using the suppressive subtractive hybridisation (SSH) method was used to analyse the differentially expressed genes between lesion and normal skin samples. Transcriptional changes of 14 genes were observed in lesion samples relative to normal skin samples. These targeted genes encoded for specific proteins which are involved in general cell function but also in different stages disrupted during the tumourigenesis process of other organisms, such as cell cycling, cell proliferation, skeletal organisation and cell migration. The results highlight transcripts that are associated with the lesion occurrence, contributing to a better understanding of the molecular aetiology of this coral trout skin disease.
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http://dx.doi.org/10.1016/j.marenvres.2016.07.009DOI Listing
September 2016

Polycomb Repressor Complex 1 Member, BMI1 Contributes to Urothelial Tumorigenesis through p16-Independent Mechanisms.

Transl Oncol 2015 Oct;8(5):387-399

Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS97TF, UK. Electronic address:

Urothelial carcinoma (UC) causes significant morbidity and remains the most expensive cancer to treat because of the need for repeated resections and lifelong monitoring for patients with non-muscle-invasive bladder cancer (NMIBC). Novel therapeutics and stratification approaches are needed to improve the outlook for both NMIBC and muscle-invasive bladder cancer. We investigated the expression and effects of B Lymphoma Mo-MLV Insertion Region 1 (BMI1) in UC. BMI1 was found to be overexpressed in most UC cell lines and primary tumors by quantitative real-time polymerase chain reaction and immunohistochemistry. In contrast to some previous reports, no association with tumor stage or grade was observed in two independent tumor panels. Furthermore, upregulation of BMI1 was detected in premalignant bladder lesions, suggesting a role early in tumorigenesis. BMI1 is not located within a common region of genomic amplification in UC. The CDKN2A locus (which encodes the p16 tumor suppressor gene) is a transcriptional target of BMI1 in some cellular contexts. In UC cell lines and primary tissues, no correlation between BMI1 and p16 expression was observed. Retroviral-mediated overexpression of BMI1 immortalized normal human urothelial cells (NHUC) in vitro and was associated with induction of telomerase activity, bypass of senescence, and repression of differentiation. The effects of BMI1 on gene expression were identified by expression microarray analysis of NHUC-BMI1. Metacore analysis of the gene expression profile implicated downstream effects of BMI1 on α4/β1 integrin-mediated adhesion, cytoskeleton remodeling, and CREB1-mediated transcription.
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http://dx.doi.org/10.1016/j.tranon.2015.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631094PMC
October 2015

Deficits in metacognitive monitoring in mathematics assessments in learners with autism spectrum disorder.

Autism 2016 May 22;20(4):463-72. Epub 2015 Jun 22.

University of Bath, UK.

Children and adults with autism spectrum disorder have been found to have deficits in metacognition that could impact upon their learning. This study explored metacognitive monitoring in 28 (23 males and 5 females) participants with autism spectrum disorder and 56 (16 males and 40 females) typically developing controls who were being educated at the same level. Participants were asked a series of mathematics questions. Based upon previous research, after each question they were asked two metacognitive questions: (1) whether they thought they had got the answer correct or not (or 'don't know') and (2) whether they meant to get the answer correct or not (or 'don't know'). Participants with autism spectrum disorder were significantly more likely than the typically developing group to erroneously think that they had got an incorrect answer correct. Having made an error, those with autism spectrum disorder were also significantly more likely to report that they had meant to make the error. Different patterns in the types of errors made were also identified between the two groups. Deficits in metacognition were identified for the autism spectrum disorder group in the learning of mathematics. This is consistent with metacognitive research from different contexts and the implications for supporting learning in autism spectrum disorder are discussed.
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http://dx.doi.org/10.1177/1362361315589477DOI Listing
May 2016

Effects of low seawater pH on the marine polychaete Platynereis dumerilii.

Mar Pollut Bull 2015 Jun 22;95(1):166-72. Epub 2015 Apr 22.

School of Biological, Biomedical and Environmental Sciences, University of Hull, Cottingham Road, Hull HU6 7RX, United Kingdom. Electronic address:

An important priority for any organism is to maintain internal cellular homeostasis including acid-base balance. Yet, the molecular level impacts of changing environmental conditions, such as low pH, remain uncharacterised. Herein, we isolate partial Na(+)/H(+)exchangers (NHE), carbonic anhydrase (CA), and calmodulin (CaM) genes from a polychaete, Platynereis dumerilii and investigate their relative expression in acidified seawater conditions. mRNA expression of NHE was significantly down-regulated after 1h and up-regulated after 7days under low pH treatment (pH 7.8), indicating changes in acid-base transport. Furthermore, the localisation of NHE expression was also altered. A trend of down regulation in CA after 1h was also observed, suggesting a shift in the CO2 and HCO3(-) balance. No change in CaM expression was detected after 7days exposure to acidified seawater. This study provides insight into the molecular level changes taking place following exposure to acidified seawater in a non-calcifying, ubiquitous, organism.
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http://dx.doi.org/10.1016/j.marpolbul.2015.04.027DOI Listing
June 2015

Emotion recognition in animated compared to human stimuli in adolescents with autism spectrum disorder.

J Autism Dev Disord 2015 Jun;45(6):1785-96

Department of Psychology, University of Bath, Bath, BA2 7AY, UK,

There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon face). Participants were 37 adolescents (age 11-16) with a diagnosis of ASD (33 male, 4 female). 42 males and 39 females served as typically developing, age-matched controls. Overall there was significant advantage for control groups over the ASD group for emotion recognition in human stimuli but not animated stimuli, across modalities. For static animated images specifically, those with ASD significantly outperformed controls. The findings are consistent with the ASD group using atypical explicit strategies.
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http://dx.doi.org/10.1007/s10803-014-2338-9DOI Listing
June 2015

Enhanced olfactory sensitivity in autism spectrum conditions.

Mol Autism 2014 20;5:53. Epub 2014 Nov 20.

Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK ; Cambridgeshire and Peterborough NHS Foundation Trust, CLASS Clinic, Cambridge, CB21 5EF UK.

Background: People with autism spectrum conditions (ASC) report heightened olfaction. Previous sensory experiments in people with ASC have reported hypersensitivity across visual, tactile, and auditory domains, but not olfaction. The aims of the present study were to investigate olfactory sensitivity in ASC, and to test the association of sensitivity to autistic traits.

Methods: We recruited 17 adult males diagnosed with ASC and 17 typical adult male controls and tested their olfactory sensitivity using the Alcohol Sniff Test (AST), a standardised clinical evaluation of olfactory detection. The AST involves varying the distance between subject and stimulus until an odour is barely detected. Participants with ASC also completed the Autism Spectrum Quotient (AQ) as a measure of autism traits.

Results: The ASC group detected the odour at a mean distance of 24.1 cm (SD =11.5) from the nose, compared to the control group, who detected it at a significantly shorter mean distance of 14.4 cm (SD =5.9). Detection distance was independent of age and IQ for both groups, but showed a significant positive correlation with autistic traits in the ASC group (r =0.522).

Conclusions: This is the first experimental demonstration, as far as the authors are aware, of superior olfactory perception in ASC and showing that greater olfactory sensitivity is correlated with a higher number of autistic traits. This is consistent with results from previous findings showing hypersensitivity in other sensory domains and may help explain anecdotal and questionnaire accounts of heightened olfactory sensitivity in ASC. Results are discussed in terms of possible underlying neurophysiology.
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http://dx.doi.org/10.1186/2040-2392-5-53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407326PMC
April 2015

Adolescents with autism spectrum disorder show a circumspect reasoning bias rather than 'jumping-to-conclusions'.

J Autism Dev Disord 2014 Mar;44(3):513-20

Department of Psychology, University of Bath, Bath, BA2 7AY, UK,

People with autism spectrum disorders (ASD) often take longer to make decisions. The Autism-Psychosis Model proposes that people with autism and psychosis show the opposite pattern of results on cognitive tasks. As those with psychosis show a jump-to-conclusions reasoning bias, those with ASD should show a circumspect reasoning bias. Jumping-to-conclusions was assessed in a sample of 20 adolescents with ASD and 23 age-matched controls using the jumping-to-conclusions beads task. Both groups demonstrated equivalent levels of confidence in decision-making, however the ASD group required more beads than controls before making their decision. Furthermore, there was a positive correlation between the beads required and degree of autism symptoms. Consistent with the Autism-Psychosis Model, a more circumspect reasoning bias was evident in ASD.
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http://dx.doi.org/10.1007/s10803-013-1897-5DOI Listing
March 2014

A full-dimensional coupled-surface study of the photodissociation dynamics of ammonia using the multiconfiguration time-dependent Hartree method.

J Chem Phys 2011 Jul;135(4):044311

Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.

Full-dimensional quantum mechanical computations are carried out to investigate the photodissociation dynamics of à state NH(3) and ND(3) using the multiconfiguration time-dependent Hartree (MCTDH) method with recently developed coupled ab initio potential energy surfaces (PESs) [Z. H. Li, R. Valero, and D. G. Truhlar, Theor. Chim. Acc. 118, 9 (2007)]. To use the MCTDH method efficiently the PESs are represented as based on the high-dimensional model representation. The à ← X̃ absorption spectra for both isotopomers were calculated for the zeroth vibrational state of the ground electronic state. With a view to treating larger systems, Jacobi coordinates are used. Computations on the coupled PES are carried out for two-, three-, five-, and six-dimensional model systems to understand the validity of reduced-dimensional calculations. In addition to the fully coupled calculations, the effect of nonadiabatic coupling on absorption spectra is shown by propagating the initial wavepacket only in the à electronic state. The calculated absorption spectra are shown to be in good agreement with available theoretical and experimental observations. Comparisons with calculations using Radau and valence coordinates show the effect of including the symmetry of the system explicitly. Finally, branching ratios for loss of a hydrogen atom via the two available channels are calculated. These predict that the nonadiabatic product increases with the dimension of the calculations and confirm the importance of the full-dimensional calculations.
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http://dx.doi.org/10.1063/1.3614038DOI Listing
July 2011

Lanthanum carbonate is an effective hypophosphatemic agent for hemodialysis patients intolerant of other phosphate binders.

J Ren Nutr 2010 Jul 2;20(4):270-7. Epub 2010 Apr 2.

Department of Nutrition and Dietetics, Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Edgbaston, Birmingham, United Kingdom.

Background: Lanthanum carbonate (LC) is a noncalcium-containing phosphate binder of proven utility in treating hyperphosphatemia in dialysis patients, and displays a good tolerability profile.

Objective: This study addressed whether this tolerability profile could result in improved phosphate control in patients intolerant of other phosphate binders, and who remain hyperphosphatemic despite intensive dietary advice and adequate dialysis provision.

Design, Setting, And Patients: This 18-month study, from a large urban hemodialysis unit, studied 55 patients identified by the multidisciplinary team as fulfilling the following criteria: persistent hyperphosphatemia; intolerance of, or admitted nonadherence to, prescribed phosphate binders (either calcium-based or sevelamer); and provision of adequate dialysis (urea reduction ratio, >65%).

Intervention And Main Outcome Measure: LC was substituted for existing phosphate binders, and results were compared between baseline and 3 months after the initiation of LC.

Results: A significant fall in phosphate level from 2.28+/-0.55mmol/L to 1.89+/-0.45mmol/L (7.06+/-1.70mg/dL to 5.85+/-1.39mg/dL) was evident 3 months after the medication switch (P < .001). This fall was associated with a significant increase in the number of patients achieving United Kingdom Renal Association guidelines for serum phosphate level (17% to 48%; P=.001). Mean phosphate-binder pill burden fell significantly by 3 months after the initiation of LC, from 7.8+/-3.4 tablets daily to 3.6+/-2.3 tablets daily. A small but significant increase also occurred in serum bicarbonate levels, from 23.3+/-2.2mmol/L (23.3+/-2.2 mEq/L) at baseline to 23.9+/-2.5mmol/L (23.9+/-2.5 mEq/L) at 3 months (P=.03). This was observed despite a prescribed reduction in dialysate bicarbonate concentration across the population (P=.03).

Conclusion: This study demonstrated the utility of LC in hemodialysis patients intolerant of alternative phosphate binders, and suggests an advantage of this agent in this patient group.
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http://dx.doi.org/10.1053/j.jrn.2009.10.009DOI Listing
July 2010

Necdin: a multi functional protein with potential tumor suppressor role?

Mol Carcinog 2009 Nov;48(11):975-81

Cancer Research UK Clinical Centre, Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom.

Necdin (NDN), a member of the melanoma-associated antigen (MAGE) family of proteins was first identified in mouse stem cells of embryonal carcinoma origin induced to differentiate by treatment with retinoic acid. The human gene maps to chromosome 15q11. This imprinted region is implicated in the pathogenesis of Prader-Willi syndrome (PWS), a neurodevelopmental disorder, where NDN is one of multiple genes silenced by deletion, maternal uniparental disomy or translocation. Due to this association, much interest has focused on the role of NDN in neuronal development and differentiation. However, a considerable number of studies have identified additional functions of NDN. Taken together these studies suggest a pleiotropic protein with diverse functions some of which may be relevant to tumorigenesis. Downregulation of NDN occurs in carcinoma cell lines and primary tumors, suggesting a tumor suppressor role. Our working hypothesis is that NDN is a worthy candidate for further studies with regard to a potential tumor suppressor role. In this article we outline the considerable evidence supporting the hypothesis that NDN has multiple functions, some of which indicate that it could be a tumor suppressor. The roles of NDN in key processes such as interaction with p53 and E2F-1, hematopoietic stem cell quiescence, transcriptional repression, angiogenesis, differentiation and interaction with the polycomb group gene BMI1 are discussed. Confirmation of NDN as a tumor suppressor may have implications for monitoring of PWS patients and could present a novel cancer therapeutic target.
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http://dx.doi.org/10.1002/mc.20567DOI Listing
November 2009

Integrated genomic and transcriptional analysis of the in vitro evolution of telomerase-immortalized urothelial cells (TERT-NHUC).

Genes Chromosomes Cancer 2009 Aug;48(8):694-710

Cancer Research UK Clinical Centre, St James's University Hospital, Leeds LS97TF, UK.

Much progress has been made in identifying the molecular genetic alterations that occur in bladder cancer. However, in many cases the genes targeted by these alterations are not known. Telomerase immortalized human urothelial cells (TERT-NHUC) are a useful resource for in vitro studies of genes involved in urothelial transformation. When cultured under standard conditions they remain genetically stable but when cultured under low-density conditions they exhibit genetic instability and acquire chromosomal alterations. TERT-NHUC from three donors were cultured at low plating density and examined at four time-points during a culture period of 600 days. Analyses included population doubling kinetics, array-based CGH (aCGH), chromosome counts, fluorescence in situ hybridization (FISH), mutation analysis, Affymetrix gene expression analysis, Western blotting for p16, anchorage-independent growth and tumorigenicity assays. Alterations acquired during continued culture of TERT-NHUC at low density (TERT-NHUC-L) included some observed in urothelial carcinoma (UC) cell lines and primary UC. Examination of gene expression in TERT-NHUC with distinct acquired genetic aberrations may pinpoint genes targeted by these alterations. Data from an aCGH study of UC cell lines and primary tumors were examined for changes in chromosomal regions that also showed alterations in TERT-NHUC-L. Loss of a region on 2q including BOK was identified in UC cell lines and primary tumors. DNER and FRAS1 were identified as potential candidate genes, whose expression is altered independently of the acquisition of any genetic event.
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http://dx.doi.org/10.1002/gcc.20672DOI Listing
August 2009

Transported to a world of emotion.

Mcgill J Med 2009 Nov 16;12(2):78. Epub 2009 Nov 16.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997255PMC
November 2009

Genes involved in differentiation, stem cell renewal, and tumorigenesis are modulated in telomerase-immortalized human urothelial cells.

Mol Cancer Res 2008 Jul;6(7):1154-68

Cancer Research UK Clinical Centre, St. James's University Hospital, Leeds LS97TF, United Kingdom.

The expression of hTERT, the catalytic subunit of telomerase, immortalizes normal human urothelial cells (NHUC). Expression of a modified hTERT, without the ability to act in telomere maintenance, did not immortalize NHUC, confirming that effects at telomeres are required for urothelial immortalization. Previous studies indicate that inhibition of telomerase has an immediate effect on urothelial carcinoma (UC) cell line viability, before sufficient divisions to account for telomere attrition, implicating non-telomere effects of telomerase in UC. We analyzed the effects of telomerase on gene expression in isogenic mortal and hTERT-transduced NHUC. hTERT expression led to consistent alterations in the expression of genes predicted to be of phenotypic significance in tumorigenesis. A subset of expression changes were detected soon after transduction with hTERT and persisted with continued culture. These genes (NME5, PSCA, TSPYL5, LY75, IGFBP2, IGF2, CEACAM6, XG, NOX5, KAL1, and HPGD) include eight previously identified as polycomb group targets. TERT-NHUC showed overexpression of the polycomb repressor complex (PRC1 and PRC4) components, BMI1 and SIRT1, and down-regulation of multiple PRC targets and genes associated with differentiation. TERT-NHUC at 100 population doublings, but not soon after transduction, showed increased saturation density and an attenuated differentiation response, indicating that these are not acute effects of telomerase expression. Some of the changes in gene expression identified may contribute to tumorigenesis. Expression of NME5 and NDN was down-regulated in UC cell lines and tumors. Our data supports the concept of both telomere-based and non-telomere effects of telomerase and provides further rationale for the use of telomerase inhibitors in UC.
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http://dx.doi.org/10.1158/1541-7786.MCR-07-2168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437422PMC
July 2008

Impaired recognition of negative basic emotions in autism: a test of the amygdala theory.

Soc Neurosci 2006 ;1(3-4):349-63

Department of Psychology, University of Essex, Colchester, UK.

Autism and Asperger Syndrome are autism spectrum conditions (ASC) characterized by deficits in understanding others' minds, an aspect of which involves recognizing emotional expressions. This is thought to be related to atypical function and structure of the amygdala, and performance by people with ASC on emotion recognition tasks resembles that seen in people with acquired amygdala damage. In general, emotion recognition findings in ASC have been inconsistent, which may reflect low numbers of participants, low numbers of stimuli and trials, heterogeneity of symptom severity within ASC groups, and ceiling effects on some tasks. The present study tested 39 male adults with ASC and 39 typical male controls on a task of basic emotion recognition from photographs, in two separate experiments. On a control face discrimination task the group with ASC were not impaired. People with ASC were less accurate on the emotion recognition task compared to controls, but only for the negative basic emotions. This is discussed in the light of similar findings from people with damage to the amygdala.
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http://dx.doi.org/10.1080/17470910601040772DOI Listing
December 2008

Fetal testosterone and empathy: evidence from the empathy quotient (EQ) and the "reading the mind in the eyes" test.

Soc Neurosci 2006 ;1(2):135-48

University of Cambridge, Cambridge, UK.

Empathy involves an understanding of what others are thinking and feeling, and enables us to interact in the social world. According to the Empathizing-Systemizing (E-S) theory, females on average have a stronger drive to empathize than males. This sex difference may in part reflect developmental differences in brain structure and function, which are themselves under the influence of fetal testosterone (fT). Previous studies have found that fT is inversely correlated with social behaviors such as eye contact in infancy, peer relationships in preschoolers, and mentalistic interpretation of animate motion. Male fetuses are exposed to higher levels of testosterone than are female fetuses. The present study investigates empathizing in children, as a function of amniotic measures of fT. One hundred ninety-three mothers of children (100 males, 93 females) aged 6-8 years of age completed children's versions of the Empathy Quotient (EQ-C), and the children themselves were tested on "Reading the Mind in the Eyes" Task (Eyes-C). All mothers had had amniocentesis during the 2nd trimester of pregnancy. There was a significant negative correlation between fT and scores on both measures. While empathy may be influenced by post-natal experience, these results suggest that pre-natal biology also plays an important role, mediated by androgen effects in the brain. These results also have implications for the causes of disabilities involving empathy, such as autism spectrum conditions, and may explain the increased rate of such conditions among males.
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http://dx.doi.org/10.1080/17470910600992239DOI Listing
December 2008
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