Clive Ballard

ICL, Londinium, England, United Kingdom

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Publications (248)1694.54 Total impact

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    ABSTRACT: To produce a practice guideline that includes a set of detailed consensus principles regarding the prescription of antipsychotics (APs) amongst people with dementia living in care homes. We used a modified Delphi consensus procedure with three rounds, where we actively specified and optimized statements throughout the process, utilizing input from four focus groups, carried out in UK, Norway, and the Netherlands. This was done to identify relevant themes and a set of statement that experts agreed upon using the Research and Development/University of California at Los Angeles (RAND/UCLA) methodology. A total of 72 scientific and clinical experts and 14 consumer experts reached consensus upon 150 statements covering five themes: (1) General prescription stipulations, (2) assessments prior to prescription, (3) care and treatment plan, (4) discontinuation, and (5) long-term treatment. In this practice guideline, novel information was provided about detailed indication and thresholds of symptoms, risk factors, circumstances at which APs should be stopped or tapered, specific criteria for justifying long-term treatment, involvement of the multidisciplinary team, and family caregiver in the process of prescription. The practice guideline is based on formal consensus of clinicians and consumer experts and provides clinicians relevant practical information that is lacking in current guidelines.
    International Psychogeriatrics 06/2015; DOI:10.1017/S1041610215000745 · 1.89 Impact Factor
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    ABSTRACT: Objectives Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Method Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. ResultsRegression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Conclusions Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright (c) 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 04/2015; 30(4). DOI:10.1002/gps.4155 · 3.09 Impact Factor
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    ABSTRACT: Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI -1.80-2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI -0.35-8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI -1.68-11.70; P = .05) and 3.63 (95% CI -1.40-8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks. This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk. Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
    Journal of the American Medical Directors Association 12/2014; 16(4). DOI:10.1016/j.jamda.2014.11.002 · 4.78 Impact Factor
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    ABSTRACT: Objective There is great interest in conducting clinical trials of disease-modifying therapies in the prodromal (early, pre-dementia), asymptomatic stages of Alzheimer's disease. Diagnostic biomarker tests offer a means of identifying prodromal patients, but it is unclear how potential participants feel about their use. Deciding whether to take part in a clinical trial is a complex process in which eligible participants must balance risks and discomforts against uncertain benefits. We sought to explore the views of potential participants through qualitative research methods. Methods Focus groups with people with early memory problems, current and former family carers explored attitudes towards participating in clinical trials in the prodromal stages of the disease, using an example of anti-amyloid antibody-therapy (immunotherapy), which are currently in development. ResultsDespite the complexities involved, almost all participants had a clear idea about whether they, personally, would like to take part. Many were highly motivated to obtain an unambiguous diagnosis, regardless of their desire to participate in a clinical trial. Participants expressed minimal concern regarding the risk of adverse events associated with immunotherapy, whereas certain tests and trial procedures provoked greater anxiety. People with memory problems were found to assess the study demands in relation to their own priorities and circumstances. Conclusions The priorities of patients might be different to clinicians and those who design and regulate clinical trials. Patient views can be used to inform the ethical debate around the disclosure of biomarker status, the design of clinical trials and the content of trial information. Copyright (c) 2013 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 12/2014; 29(1). DOI:10.1002/gps.3958 · 3.09 Impact Factor
  • Anne Corbett, Alistair Burns, Clive Ballard
    BMJ Clinical Research 11/2014; 349:g6420. DOI:10.1136/bmj.g6420 · 14.09 Impact Factor
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    Neurobiology of Aging 11/2014; 35(11):2661. DOI:10.1016/j.neurobiolaging.2014.06.016 · 4.85 Impact Factor
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    Neurobiology of Aging 11/2014; 35(11):2659. DOI:10.1016/j.neurobiolaging.2014.06.017 · 4.85 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) affects 10 million people worldwide. Half will develop psychosis, the majority experiencing hallucinations rather than delusions. Emergence of psychosis increases the likelihood of institutionalization and mortality. Where pharmacological treatment is warranted, options are limited. Most currently licensed atypical antipsychotics are ineffective or worsen motor symptoms in people with PD. This review of provides an overview of the current landscape of treatments and the opportunities in emerging research. Clozapine is the only licensed antipsychotic with proven efficacy, although the associated side effects limit its use. With recent advances in understanding the role of serotonin, rational drug design approaches have delivered a novel pharmacological treatment with recently proven efficacy in clinical trials of people with PD and psychosis. Pimavanserin represents an important addition to treatment.
    Expert Review of Clinical Pharmacology 10/2014; 7(6):1-8. DOI:10.1586/17512433.2014.966814
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    ABSTRACT: There is evidence that neurofibrillary tangle (NFT) burden is associated with psychotic symptoms in Alzheimer disease (AD). However, it is not clear whether this association is direct or mediated through the increased cognitive impairment associated with NFTs.
    Journal of the American Medical Directors Association 10/2014; 15(12). DOI:10.1016/j.jamda.2014.08.011 · 4.78 Impact Factor
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    ABSTRACT: ABSTRACT Background: The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD. Methods: We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013. Results: We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of "clinically significant A/A." There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials. Conclusions: This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.
    International Psychogeriatrics 09/2014; 27(2):1-17. DOI:10.1017/S1041610214001720 · 1.89 Impact Factor
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    Neuroscience Letters 09/2014; 580:178. DOI:10.1016/j.neulet.2014.07.057 · 2.06 Impact Factor
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    ABSTRACT: The overall objective is to determine the availability of person-centred intervention and training manuals for dementia care staff with clinical trial evidence of efficacy. Interventions were identified using a search of electronic databases, augmented by mainstream search engines, reference lists, hand searching for resources and consultation with an expert panel. The specific search for published manuals was complemented by a search for randomised control trials focussing on training and activity-based interventions for people with dementia in care homes. Manuals were screened for eligibility and rated to assess their quality, relevance and feasibility. A meta-analysis of randomised control trials indicated that person-centred training interventions conferred significant benefit in improving agitation and reducing the use of antipsychotics. Each of the efficacious packages included a sustained period of joint working and supervision with a trained mental health professional in addition to an educational element. However, of the 170 manuals that were identified, 30 met the quality criteria and only four had been evaluated in clinical trials. Despite the availability of a small number of evidence-based training manuals, there is a widespread use of person-centred intervention and training manuals that are not evidence-based. Clearer guidance is needed to ensure that commissioned training and interventions are based on robust evidence. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 08/2014; 29(8). DOI:10.1002/gps.4072 · 3.09 Impact Factor
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    ABSTRACT: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterised by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated-tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA 21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.
    Brain Pathology 08/2014; DOI:10.1111/bpa.12182 · 4.35 Impact Factor
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    ABSTRACT: Objective: To determine whether depressive symptoms are associated with medial temporal lobe atrophy in older people with and without Alzheimer disease (AD). Method: A total of 368 memory clinic patients with AD, mild cognitive impairment, and subjective cognitive impairment (SCI) were included. Depressive symptoms were defined as a score of 8 or higher on Cornell Scale for Depression in Dementia or use of antidepressant medications. Magnetic resonance imaging and computer tomography scans were rated for medial temporal lobe atrophy (MTA), using the Scheltens scale. For a subsample (n = 57 patients), hippocampal volume was manually traced. Results: Based on visual assessment, AD patients with depressive symptoms had less atrophy of the right medial temporal lobe (odds ratio [OR] for having MTA: 0.39; 95% confidence interval [CI] 0.16-0.99) and decreased scores on Scheltens scale for the left medial temporal lobe (OR: 0.43, 95% CI 0.19-0.96) in comparison to AD patients without depressive symptoms. In the subgroup where manual tracing was used to measure hippocampal volume, people with SCI experiencing depressive symptoms had smaller right (mean difference: 0.28 cm(3); P = .005) and left (mean difference 0.32 cm(3); P = .002) hippocampal volumes compared to people with SCI who did not have depressive symptoms. Conclusion: Hippocampal atrophy was more pronounced among patients having SCI with depressive symptoms, while the medial temporal lobe was less atrophic in patients having AD with depressive symptoms than those without depressive symptoms. These findings suggest that different mechanisms underlie depression in older people with and without AD and may explain some of the inconsistent observations in previous studies.
    Journal of Geriatric Psychiatry and Neurology 07/2014; 28(1). DOI:10.1177/0891988714541873 · 1.63 Impact Factor
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    ABSTRACT: People with dementia living in care homes often have complex mental health problems, disabilities and social needs. Providing more comprehensive training for staff working in care home environments is a high national priority. It is important that this training is evidence based and delivers improvement for people with dementia residing in these environments. Well-being and Health for People with Dementia (WHELD) combines the most effective elements of existing approaches to develop a comprehensive but practical staff training intervention. This optimised intervention is based on a factorial study and qualitative evaluation, to combine: training on person-centred care, promoting person-centred activities and interactions, and providing care home staff and general practitioners with updated knowledge regarding the optimal use of psychotropic medications for persons with dementia in care homes.
    Trials 07/2014; 15(1):284. DOI:10.1186/1745-6215-15-284 · 2.12 Impact Factor
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    ABSTRACT: Introduction: Alzheimer's disease (AD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) together account for the vast majority of individuals with dementia. Approximately 35 million people worldwide are affected with this condition, and despite decades of research, effective therapies that slow or reverse disease progression have not yet been developed. The recent failure of several large-scale clinical trials is beginning to challenge the magnitude of focus on amyloid-related therapies for AD, and newer drug targets that have shown promise in the laboratory are being investigated in clinical trials. Areas covered: This review summarises the current understanding of the underlying biology of AD, PDD and DLB and outlines the most recent drug candidates in advanced clinical trials. Expert opinion: The lack of success in drug discovery for disease-modifying therapies for AD, PDD and DLB can be attributed to limitations in the design of clinical trials and the narrow focus of molecular targets for treatment. New avenues for drug discovery including repositioning and novel target identification may now provide opportunities for success, provided a critical mass of clinical trials is achieved through increased investment.
    Expert Opinion on Pharmacotherapy 07/2014; 15(13):1-14. DOI:10.1517/14656566.2014.936848 · 3.09 Impact Factor
  • Clive Ballard, Anne Corbett, Robert Howard
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    ABSTRACT: Gerhard et al clarify our understanding of mortality associated with antipsychotic use in people with dementia, by demonstrating a clear dose relationship and highlighting key questions regarding the relative mortality risk of different atypical antipsychotics. The study also suggests that antipsychotics may confer risks of increased mortality in older people without dementia.
    The British journal of psychiatry: the journal of mental science 07/2014; 205(1):4-5. DOI:10.1192/bjp.bp.113.128710 · 7.34 Impact Factor
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    ABSTRACT: Objective: To investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods: 75 patients with DLB and PDD were included in a prospective double-blinded randomised placebo-controlled trial (RCT) of memantine, of whom long-term follow-up was available for 42. Treatment response was recorded 24 weeks from baseline and measured by Clinical Global Impression of Change (CGIC). The participants were grouped as responders (CGIC 1-3) or non-responders (CGIC 4-7). The 24-week RCT was followed by open-label treatment and survival was recorded at 36 months. Results: After 36-month follow-up, patients in the memantine group had a longer length of survival compared with patients in the placebo group (log rank x(2)=4.02, p=0.045). Within the active treatment group, survival analysis 36 months from baseline showed that the memantine responders, based on CGIC, had higher rates of survival compared with the non-responders (log rank x(2)=6.595, p=0.010). Similar results were not seen in the placebo group. Conclusions: Early treatment with memantine and a positive clinical response to memantine predicted longer survival in patients with DLB and PDD. This suggests a possible disease-modifying effect and also has implications for health economic analysis. However, owing to the small study sample, our results should merely be considered as generating a hypothesis which needs to be evaluated in larger studies.
    BMJ Open 07/2014; 4(7):e005158. DOI:10.1136/bmjopen-2014-005158 · 2.06 Impact Factor
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    ABSTRACT: The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid β (Aβ), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Aβ (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn(2+) modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD.
    Neurobiology of Aging 06/2014; 35(12). DOI:10.1016/j.neurobiolaging.2014.06.015 · 4.85 Impact Factor
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    ABSTRACT: Objective: to describe the prevalence and severity of dementia, depression, behavioural problems and relevant medication use in a representative sample of residential and nursing care home residents. Design/setting: a survey conducted in 15 randomly selected South East London care homes. Consensus clinical dementia diagnoses were made from multi-source information, and the Clinical Dementia Rating (CDR) Scale applied. Depression was ascertained using the Cornell Depression in Dementia Scale and psychological/behavioural problems using the Neuropsychiatric Inventory (NPI). Participants: three hundred and one residents with a mean (SD) age of 83.5 (9.8) and 65.8% female were included. Results: dementia (CDR 1-3) prevalence was 75.1% overall, 55.8% in residential homes, 91.0% in residential elderly mentally infirm care and 77.0% in nursing homes. Depression prevalences were 26.5, 22.0 and 29.6%, respectively, and mean (95% CI) NPI severity scores 3.99 (3.47-4.50), 6.34 (5.29-7.39) and 6.10 (5.50-6.70) with 87.3% of the sample exhibiting at least one NPI symptom. Antidepressants were prescribed in 25.6, 25.0 and 41.3%, respectively, and antipsychotics in 7.0, 34.1 and 19.1%. Conclusion: dementia is substantially more common in care homes than recorded diagnoses would suggest, but studies using brief screening instruments may overestimate prevalence. High prevalences of depressive and/or behavioural symptoms and psychotropic use suggest significant unmet need.
    Age and Ageing 05/2014; 43(4). DOI:10.1093/ageing/afu062 · 3.11 Impact Factor

Publication Stats

7k Citations
1,694.54 Total Impact Points


  • 2008–2015
    • ICL
      Londinium, England, United Kingdom
    • Northumberland, Tyne and Wear NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
    • University of Bergen
      • Institute of Medicine
      Bergen, Hordaland Fylke, Norway
  • 2004–2015
    • King's College London
      • • Wolfson Centre for Age-Related Diseases
      • • Institute of Psychiatry
      Londinium, England, United Kingdom
  • 2005–2014
    • Stavanger University Hospital
      • Department of Neurology
      Stavenger, Rogaland, Norway
  • 2008–2013
    • The Kings College
      Brooklyn, New York, United States
  • 2005–2012
    • The Alzheimers Society
      Londinium, England, United Kingdom
  • 2011
    • The King's College
      Charlotte, North Carolina, United States
    • The University of Manchester
      • Mental Health and Neurodegeneration Research Group
      Manchester, ENG, United Kingdom
    • University of Antwerp
      Antwerpen, Flemish, Belgium
  • 1997–2007
    • Newcastle University
      • Institute for Ageing and Health
      Newcastle-on-Tyne, England, United Kingdom
  • 2006
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
    • University of Hull
      Kingston upon Hull, England, United Kingdom
  • 2001–2006
    • Newcastle University Medicine Malaysia
      Bharu, Johor, Malaysia
    • Royal College of Psychiatrists
      Londinium, England, United Kingdom
  • 1997–2004
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Department of Neurology
      Newcastle-on-Tyne, England, United Kingdom
  • 1999
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1995
    • University of Birmingham
      Birmingham, England, United Kingdom