Publications
687 results found
Belgrave D, Custovic A, 2016, The importance of being earnest in epidemiology, Acta Paediatrica, Vol: 105, Pages: 1384-1386, ISSN: 0803-5253
Del Giacco SR, Bakirtas A, Bel E, et al., 2016, Allergy in severe asthma, Allergy, Vol: 72, Pages: 207-220, ISSN: 0105-4538
It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma.
Belgrave D, Simpson A, Custovic A, 2016, Allergen-specific biomarkers to distinguish severe asthma endotypes, European Academy of Allergy and Clinical Immunology Congress, Publisher: Wiley, Pages: 6-6, ISSN: 0105-4538
Deliu M, Yavuz ST, Sperrin M, et al., 2016, Hierarchical clustering identifies novel subgroups of childhood asthma, European Academy of Allergy and Clinical Immunology Congress, Publisher: Wiley, Pages: 98-98, ISSN: 0105-4538
Roberts G, Ollert M, Aalberse R, et al., 2016, A new framework for the interpretation of IgE sensitization tests, Allergy, Vol: 71, Pages: 1540-1551, ISSN: 1398-9995
IgE sensitization tests, such as skin prick testing and serum specific IgE, have been used to diagnose IgE-mediated clinical allergy for many years. Their prime drawback is that they detect sensitization which is only loosely related to clinical allergy. Many patients therefore require provocation tests to make a definitive diagnosis; these are often expensive and potentially associated with severe reactions. The likelihood of clinical allergy can be semi-quantified from an IgE sensitization test results. This relationship varies though according to the patients’ age, ethnicity, nature of the putative allergic reaction and co-existing clinical diseases such as eczema. The likelihood of clinical allergy can be more precisely estimated from an IgE sensitization test result, by taking into account the patient's presenting features (pre-test probability). The presence of each of these patient specific factors may mean that a patient is more or less likely to have clinically allergy with a given test result (post-test probability). We present two approaches to including pre-test probabilities in the interpretation of results. These approaches are currently limited by a lack of data to allow us to derive pre-test probabilities for diverse setting, regions and allergens. Also, co-factors, such as exercise, may be necessary for exposure to an allergen to result in an allergic reaction in specific IgE positive patients. The diagnosis of IgE-mediated allergy is now being aided by the introduction of allergen component testing which may identify clinically relevant sensitization. Other approaches are in development with basophil activation testing being closest to clinical application.
Bousquet J, Farrell J, Crooks G, et al., 2016, Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)., Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
Deliu M, Sperrin M, Belgrave D, et al., 2016, Identification of Asthma Subtypes Using Clustering Methodologies., Pulmonary Therapy, Vol: 2, Pages: 19-41, ISSN: 2364-1754
Asthma is a heterogeneous disease comprising a number of subtypes which may be caused by different pathophysiologic mechanisms (sometimes referred to as endotypes) but may share similar observed characteristics (phenotypes). The use of unsupervised clustering in adult and paediatric populations has identified subtypes of asthma based on observable characteristics such as symptoms, lung function, atopy, eosinophilia, obesity, and age of onset. Here we describe different clustering methods and demonstrate their contributions to our understanding of the spectrum of asthma syndrome. Precise identification of asthma subtypes and their pathophysiological mechanisms may lead to stratification of patients, thus enabling more precise therapeutic and prevention approaches.
Lin L, Belgrave D, Bakhsoliani E, et al., 2016, Phenotyping immune responses In asthma and respiratory infections, American Thoracic Society 2016 International Conference, Publisher: American Thoracic Society, ISSN: 1535-4970
Bousquet J, Schünemann HJ, Hellings PW, et al., 2016, MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis, Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 367-374.e2, ISSN: 1097-6825
The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.
Bousquet J, Barbara C, Bateman E, et al., 2016, AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from concept to implementation, European Respiratory Journal, Vol: 47, Pages: 1028-1033, ISSN: 0903-1936
Castro-Rodriguez JA, Custovic A, Ducharme FM, 2016, Treatment of asthma in young children: evidence-based recommendations, Asthma Research and Practice, Vol: 2, ISSN: 2054-7064
In the present review, we focus on evidence-based data for the use of inhaled corticosteroids (ICS), leukotriene receptor antagonist (LTRA), long-acting beta2-agonits (LABA) and oral corticosteroids (OCS), with a special emphasis on well-performed randomized clinical trials (RCTs) and meta-analyses of such trials for the chronic management of asthma/wheeze in infants and preschoolers. RESULTS: Seven meta-analyses and 14 RCTs were reviewed. Daily ICS should be the preferred drug for infants/preschoolers with recurrent wheezing, especially in asthmatics. For those with moderate or severe episodes of EVW, the use of high intermittent ICS doses significantly reduce the use of OCS. There is no evidence of effect of intermittent ICS at low-moderate dose in preschoolers with mild EVW episodes. In preschoolers with asthma, there were no significant differences between daily vs. intermittent ICS in terms of asthma exacerbations with insufficient power to conclude to equivalence; however, for other asthma control outcomes, daily ICS works significantly better than intermittent ICS for older children. Daily ICS is superior to daily or intermittent LRTA for reducing symptoms, preventing exacerbations, and improving lung function. No RCTs testing combination therapy with ICS and LABA (or LTRA) were published in infant/preschoolers. Parent-initiation of OCS at the first sign of symptoms is not effective in children with recurrent wheezing episode. In terms of ICS safety, growth suppression is dose and molecule-dependent but it's effect is not cumulative beyond the first year of therapy and may be associated with some catch-up growth while on or off therapy. Linear growth must be monitored as individual susceptibility to ICS drugs may vary considerably.
Mohammad HR, Belgrave D, Kopec Harding K, et al., 2016, Age, sex, and the association between skin test responses and IgE titres with asthma., Pediatric Allergy and Immunology, Vol: 27, Pages: 313-319, ISSN: 1399-3038
BACKGROUND: Skin prick tests (SPTs) and allergen-specific serum IgE (sIgE) measurements are the main diagnostic tools for confirming atopic sensitization. Results are usually reported as "positive" or "negative", using the same arbitrary cut-offs (SPT>3mm, sIgE>0.35 kUA /L) across different ages and sexes. We investigated the influence of age and sex on the interpretation of allergy test in the context of childhood asthma. METHODS: In a population-based birth cohort (n=1051), we ascertained the information on asthma/wheeze (validated questionnaires), and performed SPTs and sIgE measurement to inhalant allergens (dust mite, cat, dog) at follow-ups between ages three and 11 years. We investigated the association between quantitative sensitisation (sum of SPT mean wheal diameters [MWD] and sIgE titres to the three allergens) and current wheeze and asthma across ages and sexes. RESULTS: We observed a significant association between the SPT MWD and sIgE titres and wheeze/asthma at most ages and for both sexes. However, the strength of this association was age and sex-dependent. For SPTs, the strength of the association between MWD and asthma increased with increasing age; we observed the opposite pattern for sIgE titre. For any given SPT MWD/sIgE titre, boys were significantly more likely to express clinical symptoms, particularly in early life; this difference between males and females diminished with age, and was no longer significant by age 11 years. CONCLUSIONS: Age and sex should be taken into account when interpreting the results of skin tests and sIgE measurement, and age- and sex-specific normative data are needed for these allergy tests. This article is protected by copyright. All rights reserved.
DeVries A, Wlasiuk G, Miller SJ, et al., 2016, Neonatal Smad3 Promoter Hypermethylation Predicts Asthma In Children Of Asthmatic Mothers From Three Birth Cohorts, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Sathe SK, Liu C, Zaffran VD, 2016, Food Allergy, ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY, VOL 7, Editors: Doyle, Klaenhammer, Publisher: ANNUAL REVIEWS, Pages: 191-220
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- Citations: 55
Sumner H, Begum H, Simpson A, et al., 2015, THE PRACTICALITIES OF USING ALLERGEN-IMPERMEABLE BED COVERS IN CHILDREN WITH MITE ALLERGIC ASTHMA, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A122-A122, ISSN: 0040-6376
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Wang R, Sperrin M, Prosperi M, et al., 2015, Differing in symptomology dimension in different foods: an exploratory analysis of double-blind placebo-controlled food challenges using principle component analysis, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 1877-1878, ISSN: 0954-7894
Felix JF, Bradfield JP, Monnereau C, et al., 2015, Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index., Human Molecular Genetics, Vol: 25, Pages: 389-403, ISSN: 1460-2083
A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
Wu J, Prosperi MC, Simpson A, et al., 2015, Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts, Clinical and Experimental Allergy, Vol: 45, Pages: 1801-1811, ISSN: 1365-2222
BACKGROUND: Models that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma. OBJECTIVE: To characterize the patterns of peripheral blood mononuclear cells' (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population-based birth cohorts using machine learning techniques. METHODS: PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 μg/ml). Cytokine expression (IL-13, IL-5, IFN-γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping. RESULTS: A six-class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: 'Nonresponders' (n = 905, 55%); 'IL-10 responders' (n = 49, 3%); 'IFN-γ and IL-13 medium responders' (n = 56, 3.4%); 'IL-13 medium responders' (n = 351, 21.4%); 'IL-5 and IL-13 medium responders' (n = 77, 4.7%); and 'IL-13 and IL-5 high responders' (n = 204, 12.4%). 'IL-13 and IL-5 high responders' were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma. CONCLUSION: Using model-based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL-13 and IL-5), and clinical outcomes. 'IL-13 and IL-5 high responders' class was strongly associated with HDM sensitization. However, among HDM-sensitized children, one-third showed no PBMC response to HDM, and the
Bousquet J, Schunemann HJ, Fonseca J, et al., 2015, MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation, Allergy, Vol: 70, Pages: 1372-1392, ISSN: 0105-4538
Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
Holt PG, Strickland D, Bosco A, et al., 2015, Distinguishing benign from pathologic TH2 immunity in atopic children., Journal of Allergy and Clinical Immunology, Vol: 137, Pages: 379-387, ISSN: 1097-6825
BACKGROUND: Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms. OBJECTIVE: We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children. METHODS: In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass. RESULTS: Among mite-sensitized children across all populations and at different ages, house dust mite-specific IgG/IgE ratios (but not IgG4/IgE ratios) were significantly lower in children with asthma compared with ratios in those without asthma and lowest among the most severely symptomatic. This finding was mirrored by relationships between rhinitis and antibody responses to grass. Depending on age/allergen specificity, 20% to 40% of children with allergen-specific IgE (sIgE) of 0.35 kU/L or greater had negative skin test responses, and these children also expressed the high sIgG/sIgE immunophenotype. sIgG1 from these children inhibited allergen-induced IgE-dependent basophil activation in a dose-dependent fashion. Profiling of aeroallergen-specific CD4(+) TH memory responses revealed positive associations between sIgG/sIgE ratios and IL-10-dependent gene signatures and significantly higher IL-10/TH2 cytokine (protein) ratios among nonsymptomatic children. CONCLUSION: In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor. We posit that its production during allergen-induced memory responses contributes significantly to attenuation of inflammation through promoting IgG1-mediated damping of the FcεR
Paternoster L, Standl M, Waage J, et al., 2015, Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis, Nature Genetics, Vol: 47, Pages: 1449-1456, ISSN: 1546-1718
Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.
Belgrave DC, Simpson A, Buchan IE, et al., 2015, Atopic dermatitis and respiratory allergy: what is the link, Current Dermatology Reports, Vol: 4, Pages: 221-227, ISSN: 2162-4933
Understanding the aetiology and progression of atopic dermatitis and respiratory allergy may elucidate early preventative and management strategies aimed towards reducing the global burden of asthma and allergic disease. In this article, we review the current opinion concerning the link between atopic dermatitis and the subsequent progression of respiratory allergies during childhood and into early adolescence. Advances in machine learning and statistical methodology have facilitated the discovery of more refined definitions of phenotypes for identifying biomarkers. Understanding the role of atopic dermatitis in the development of respiratory allergy may ultimately allow us to determine more effective treatment strategies, thus reducing the patient and economic burden associated with these conditions.
Waage JE, Standl M, Paternoster L, et al., 2015, A genome-wide association study of allergic rhinitis in 216 361 individuals identifies several novel susceptibility loci and increases knowledge on genetic pathways and cell types involved in disease etiology, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: Wiley, Pages: 108-108, ISSN: 0105-4538
Waage JE, Kreiner-Moller E, Standl M, et al., 2015, Shared genetic origins of allergy and autoimmune diseases, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: Wiley, Pages: 112-112, ISSN: 0105-4538
Murray CS, Sumner H, Mycock M, et al., 2015, Preventing asthma exacerbations by allergen-impermeable bed covers in children: double-blind randomised placebo controlled trial, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 75-75, ISSN: 0105-4538
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- Citations: 2
Kuklinska-Pijanka A, Fuller N-J, Custovic A, et al., 2015, Environmental analysis of specific peanut allergens in house dust indicates high prevalence of Ara h 2 and Ara h 6, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 265-266, ISSN: 0105-4538
Downs ML, Simpson A, Custovic A, et al., 2015, Insoluble and soluble roasted walnut proteins retain antibody reactivity, Food Chemistry, Vol: 194, Pages: 1013-1021, ISSN: 1873-7072
Thermal processing techniques commonly used during food production have the potential to impact food allergens by inducing physical and/or chemical changes to the proteins. English walnuts (Juglans regia) are among the most commonly allergenic tree nuts, but little information is available regarding how walnut allergens respond to thermal processing. This study evaluated the effects of dry roasting (132 or 180 °C for 5, 10, or 20 min) on the solubility and immunoreactivity of walnut proteins. A dramatic decrease in walnut protein solubility was observed following dry roasting at 180 °C for 20 min. However, both the soluble and insoluble protein fractions from roasted walnuts maintained substantial amounts of IgG immunoreactivity (using anti-raw and anti-roasted walnut antisera), with similar patterns of reactivity observed for human IgE from walnut-allergic individuals. Thus, walnut proteins are relatively stable under certain thermal processing conditions, and IgE reactivity remains present even when insoluble aggregates are formed.
Custovic A, Ainsworth J, Arshad H, et al., 2015, The Study Team for Early Life Asthma Research (STELAR) consortium 'Asthma e-lab': team science bringing data, methods and investigators together, Thorax, Vol: 70, Pages: 799-801, ISSN: 0040-6376
We created Asthma e-Lab, a secure web-based researchenvironment to support consistent recording, descriptionand sharing of data, computational/statistical methods andemerging findings across the five UK birth cohorts. The eLabserves as a data repository for our unified dataset andprovides the computational resources and a scientific socialnetwork to support collaborative research. All activities aretransparent, and emerging findings are shared via the eLab,linked to explanations of analytical methods, thusenabling knowledge transfer. eLab facilitates the iterativeinterdisciplinary dialogue between clinicians, statisticians,computer scientists, mathematicians, geneticists and basicscientists, capturing collective thought behind theinterpretations of findings
Guerra S, Halonen M, Vasquez MM, et al., 2015, Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study, LANCET RESPIRATORY MEDICINE, Vol: 3, Pages: 613-620, ISSN: 2213-2600
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- Citations: 114
Howard R, Rattray M, Prosperi M, et al., 2015, Distinguishing Asthma Phenotypes Using Machine Learning Approaches, CURRENT ALLERGY AND ASTHMA REPORTS, Vol: 15, ISSN: 1529-7322
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- Citations: 71
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