Publications
451 results found
Rosenfeld M, Cunningham S, Harris WT, et al., 2019, An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB)., Journal of Cystic Fibrosis, Vol: 18, Pages: 838-843, ISSN: 1569-1993
BACKGROUND: KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI. METHODS: Children received age- and weight-based ivacaftor dosages for 84 weeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function. RESULTS: All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84 weeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3 × upper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8 × ULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters. CONCLUSIONS: Ivacaftor was generally well tolerated for up to 108 weeks in children aged 2 to 5 years with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24 weeks of treatment were maintained for up to an additional 84 weeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension.
Martin AD, Davis P, Davies JC, et al., 2019, DEVELOPMENT OF A RAPID POINT-OF-CARE DIAGNOSTIC IMMUNOASSAY FOR THE DETECTION OF P. AERUGINOSA IN CYSTIC FIBROSIS PATIENTS, North American Cystic Fibrosis Conference, Publisher: WILEY, Pages: S291-S292, ISSN: 8755-6863
Murphy RA, Christiansen S, Sabnis A, et al., 2019, GLATIRAMER ACETATE IS AN ANTIBIOTIC RESISTANCE BREAKER AGAINST CYSTIC FIBROSIS STRAINS OF PSEUDOMONAS AERUGINOSA VIA DISRUPTION OF THE BACTERIAL OUTER MEMBRANE, North American Cystic Fibrosis Conference, Publisher: WILEY, Pages: S297-S298, ISSN: 8755-6863
Bayfield KJ, Horsley A, Alton E, et al., 2019, Simultaneous sulfur hexafluoride and nitrogen multiple-breath washout (MBW) to examine inherent differences in MBW outcomes, ERJ Open Research, Vol: 5, ISSN: 2312-0541
Multiple-breath washout (MBW) can be performed with different gases (sulfur hexafluoride (SF6-) and nitrogen (N2)) and different devices, all of which give discrepant results. This study aimed to confirm previously reported differences and explore factors influencing discrepant results; equipment factors or the physical properties of gases used. Methods: Healthy controls (HCs) and participants with cystic fibrosis (CF) completed MBW trials on two commercially available devices (Exhalyzer D (N2) and Innocor (SF6)). Simultaneous washout of both gases at the same time on the commercial equipment and simultaneous washouts using a respiratory mass spectrometer (RMS) were completed in subsets. Primary outcomes were lung clearance index (LCI), breath number and time required to washout. Results: Breath number was higher with N2 washout than SF6 in both HCs and patients with CF, whether washouts were completed individually or simultaneously. The difference was greater in more advanced disease, largely caused by differences in the final part of the washout. Results from commercial devices were similar to those obtained with the RMS. Conclusions: N2 MBW results were higher than SF6 MBW, with some of the largest differences reported to date being observed. The biggest impact was at the end of the washout and this was even the case when gases were washed out simultaneously. N2 and SF6 MBW results are inherently different and should be considered as independent measurements.
Waller MD, Harman K, Bayfield KJ, et al., 2019, OPPORTUNISTIC ASSESSMENT OF UPPER AND LOWER AIRWAY ELECTROPHYSIOLOGY AND LUNG FUNCTION IN CYSTIC FIBROSIS, North American Cystic Fibrosis Conference, Publisher: WILEY, Pages: S163-S163, ISSN: 8755-6863
Davies JC, Scott S, Dobra R, et al., 2019, Fair selection of participants in clinical trials: The challenge to push the envelope further, Journal of Cystic Fibrosis, Vol: 18, Pages: e48-e50, ISSN: 1569-1993
Davies JC, Drevinek P, Elborn JS, et al., 2019, Speeding up access to new drugs for CF: Considerations for clinical trial design and delivery, Journal of Cystic Fibrosis, Vol: 18, Pages: 677-684, ISSN: 1569-1993
The last decade has witnessed developments in the CF drug pipeline which are both exciting and unprecedented, bringing with them previously unconsidered challenges. The Task Force group was brought together to consider these challenges and possible strategies to address them. Over the last 18 months, we have discussed internally and gathered views from a broad range of individuals representing patient organisations, clinical and research teams, the pharmaceutical industry and regulatory agencies. In this and the accompanying article, we discuss two main areas of focus: i) optimising trial design and delivery for speed and efficiency; ii) drug development for patients with rare CFTR mutations. We propose some strategies to tackle the challenges ahead and highlight areas where further thought is needed. We see this as the start of a process rather than the end and hope herewith to engage the wider community in seeking solutions to improved treatments for all patients with CF.
Amaral MD, de Boeck K, on behalf of the ECFS Strategic Planning Task Force on Speeding up access to new drugs for CF, et al., 2019, Theranostics by testing CFTR modulators in patient-derived materials: The current status and a proposal for subjects with rare CFTR mutations, Journal of Cystic Fibrosis, Vol: 18, Pages: 685-692, ISSN: 1569-1993
The last decade has witnessed developments in the CF drug pipeline which are both exciting and unprecedented, bringing with them previously unconsidered challenges. The Task Force group came together to consider these challenges and possible strategies to address them. Over the last 18 months, we have discussed internally and gathered views from a broad range of individuals representing patient organizations, clinical and research teams, the pharmaceutical industry and regulatory agencies. In this and the accompanying article, we discuss two main areas of focus: i) optimising trial design and delivery for speed/efficiency; ii) drug development for patients with rare CFTR mutations. We propose some strategies to tackle the challenges ahead and highlight areas where further thought is needed. We see this as the start of a process rather than the end and hope herewith to engage the wider community in seeking solutions to improved treatments for all patients with CF.
Dobra R, Scott S, Davies JC, et al., 2019, Who and why; sharing our experiences of developing a standard operating procedure (SOP) to allocate screening slots for highly competitive cystic fibrosis trials, Journal of Cystic Fibrosis, Vol: 18, Pages: e45-e46, ISSN: 1569-1993
Davies JC, Van de Steen O, van Koningsbruggen-Rietschel S, et al., 2019, GLPG1837, a CFTR potentiator, in p.Gly551Asp (G551D)-CF patients: An open-label, single-arm, phase 2a study (SAPHIRA1)., Journal of Cystic Fibrosis, Vol: 18, Pages: 693-699, ISSN: 1569-1993
BACKGROUND: Investigation of novel cystic fibrosis transmembrane conductance regulator (CFTR) potentiators, such as GLPG1837, for CF patients with gating mutations is challenging as trials require patients to withhold ivacaftor, the current standard of care. This study explored the feasibility of such a study and the impact of one-week ivacaftor withdrawal. METHODS: This open-label, single-arm study aimed to enrol 32 adults ≥18 years of age with CF and at least one p.Gly551Asp (G551D) mutation. Patients received three increasing GLPG1837 dosages twice-daily for two 7-day and one 14-day period following a one-week ivacaftor washout. The primary outcome was safety; secondary outcomes were changes in sweat chloride concentration, spirometry outcomes, and pharmacokinetics. RESULTS: Twenty-six patients enrolled; 24 completed the study. Adverse events were reported by 53.8-76.9% of patients (dosage-dependent), with respiratory adverse events most common. Mean sweat chloride concentrations decreased from 97.7 mmol/L (baseline) to 68.7 mmol/L (end of GLPG1837 treatment). In ivacaftor-pre-treated patients, mean sweat chloride concentrations rose from 42.5 mmol/L at screening to 98.5 mmol/L after ivacaftor washout. Levels were decreased following GLPG1837 treatment (to 68.8 mmol/L at treatment end). Percent predicted forced expiratory volume in 1 s declined from 73.3% at screening to 68.5% after ivacaftor washout but returned to screening level at treatment end (73.1%). CONCLUSIONS: Patient willingness to participate in the study suggests that the need for a short period of ivacaftor withdrawal may not be a barrier to development of novel potentiators, such as GLPG1837. A one-week ivacaftor washout was generally well tolerated, but resulted in a decline in lung function, which was reversed with GLPG1837 treatment to pre-washout levels. Combined with the concentration-dependent decrease in sweat chloride concentration, results show that GLPG1837 increases CFTR activity in G
Dobra R, Madge S, Martin I, et al., 2019, "Fortunate are those who take the first steps"? The psychosocial impact of novel drug development., Paediatric Respiratory Reviews, Vol: 31, Pages: 9-11, ISSN: 1526-0542
Novel drug development offers people with cystic fibrosis exciting opportunities but is not without challenges. Currently, there is an understandable emphasis on protecting patients' physical health when developing treatments. However, there appears to be little consideration of how novel drug development impacts on psychosocial wellbeing, or the downstream consequences of this. Using an illustrative case and reviewing the literature we explore themes regarding the psychosocial impact of trial participation and novel drug development and identify areas requiring further research. Through this, we hope to prepare healthcare professionals to better understand the needs of their patients in this rapidly evolving landscape.
Davies JC, 2019, Trials and tribulations: The highs and lows of running cystic fibrosis drug studies, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 31, Pages: 25-27, ISSN: 1526-0542
- Author Web Link
- Cite
- Citations: 1
Chilvers M, Davies JC, Ratjen F, et al., 2019, WS12-4 Long-term safety and efficacy of lumacaftor/ivacaftor therapy in patients aged 6–11 years with cystic fibrosis homozygous for the F508del-CFTR mutation (F/F), Journal of Cystic Fibrosis, Vol: 18, Pages: S23-S23, ISSN: 1569-1993
Ahmed B, Cox M, Cuthbertson L, et al., 2019, Longitudinal development of the airway microbiota in infants with cystic fibrosis, Scientific Reports, Vol: 9, ISSN: 2045-2322
The pathogenesis of airway infection in cystic fibrosis (CF) is poorly understood. We performed a longitudinal study coupling clinical information with frequent sampling of the microbiota to identify changes in the airway microbiota in infancy that could underpin deterioration and potentially be targeted therapeutically. Thirty infants with CF diagnosed on newborn screening (NBS) were followed for up to two years. Two hundred and forty one throat swabs were collected as a surrogate for lower airway microbiota (median 35 days between study visits) in the largest longitudinal study of the CF oropharyngeal microbiota. Quantitative PCR and Illumina sequencing of the 16S rRNA bacterial gene were performed. Data analyses were conducted in QIIME and Phyloseq in R. Streptococcus spp. and Haemophilus spp. were the most common genera (55% and 12.5% of reads respectively) and were inversely related. Only beta (between sample) diversity changed with age (Bray Curtis r2 = 0.15, P = 0.03). Staphylococcus and Pseudomonas were rarely detected. These results suggest that Streptococcus spp. and Haemophilus spp., may play an important role in early CF. Whether they are protective against infection with more typical CF micro-organisms, or pathogenic and thus meriting treatment needs to be determined.
Filloux A, Davies JC, 2019, Chronic infection by controlling inflammation, NATURE MICROBIOLOGY, Vol: 4, Pages: 378-379, ISSN: 2058-5276
Keating D, Davies J, Moskowitz S, et al., 2019, PHASE 2 SAFETY AND EFFICACY: CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) MODULATOR REGIMEN VX-659/TEZACAFTOR(TEZ)/IVACAFTOR(IVA), Publisher: WILEY, Pages: 68-68, ISSN: 1323-7799
Davies G, Griesenbach U, Alton E, et al., 2019, 53 - Molecular Therapies for Cystic Fibrosis, Kendig's Disorders of the Respiratory Tract in Children, Pages: 800-811.e3, ISBN: 9780323448871
This chapter describes the therapeutic strategies for cystic fibrosis which are based on targeting cystic fibrosis transmembrane conductance regulator (CFTR), either at the gene or protein level. We provide updates on small molecule CFTR modulators and gene therapy, focusing on clinical development and evaluation. The field has seen significant progress over recent years, particularly with the CFTR potentiator, ivacaftor, in patients with class III mutations. Increased understanding of the abnormalities in the structure and function of CFTR protein will help optimize the approaches required for normalizing function and, in doing so, aid the rational design of clinical trials-both in terms of the development of more efficacious drugs and the selection of appropriate patient populations. While progress with gene therapy remains some way behind, potential benefits (including being mutation agnostic and a nonsystemic route of delivery) remain significant. It may be that future optimal approaches will harness the benefits of more than one of these approaches and lead to considerable synergy. The ultimate goal for molecular and advanced therapies in cystic fibrosis is to find drugs or combinations of drugs capable of restoring CFTR function, applicable to patients with any genetic mutation.
Davies G, Griesenbach U, Alton E, et al., 2019, Molecular Therapies for Cystic Fibrosis, Kendig's Disorders of the Respiratory Tract in Children, Publisher: Elsevier, Pages: 800-811.e3
Simmonds NJ, Pabary R, Kohlhaufl J, et al., 2018, THE ADDED VALUE OF NASAL POTENTIAL DIFFERENCE MEASUREMENT WHEN FIRST-LINE CYSTIC FIBROSIS (CF) INVESTIGATIONS ARE NON-DIAGNOSTIC, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A84-A85, ISSN: 0040-6376
Dobra R, Edmondson C, Hughes D, et al., 2018, Potentiators and Correctors in Paediatric Cystic Fibrosis Patients: A Narrative Review, PEDIATRIC DRUGS, Vol: 20, Pages: 555-566, ISSN: 1174-5878
Davies JC, Moskowitz SM, Brown C, et al., 2018, VX-659-Tezacaftor-Ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles, New England Journal of Medicine, Vol: 379, Pages: 1599-1611, ISSN: 0028-4793
BackgroundThe next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659–tezacaftor–ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis.MethodsWe evaluated the effects of VX-659–tezacaftor–ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659–tezacaftor–ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del–MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del–Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1).ResultsVX-659–tezacaftor–ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659–tezacaftor–ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659–tezacaftor–ivacaftor resulted in significant mean increases in the percentage of predicted FEV1 through day 29 (P<0.001) of up to 13.3 points in patients with Phe508del–MF genotypes; in patients with the Phe508del–Phe508del genotype already receiving tezacaftor–ivacaftor, adding VX-659 resulted in a further 9.7-point increase in the percentage of predicted FEV1. The sweat chloride concentrations and scores on the respiratory domain of the Cystic Fibrosis Questionnaire–Revised improved in both patient populations.ConclusionsRobust in vitro activity of VX-659–tezacaftor–ivacaftor t
Wertheim D, Olden C, Symes L, et al., 2018, Home monitoring of respiratory rate from pulse oximetry in children with cystic fibrosis, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Thursfield RM, Naderi K, Leaver N, et al., 2018, Children with cystic fibrosis demonstrate no respiratory immunological, infective or physiological, consequences of vitamin D deficiency, Journal of Cystic Fibrosis, Vol: 17, Pages: 657-665, ISSN: 1569-1993
BACKGROUND: Vitamin D has health benefits in many respiratory diseases but the evidence in CF is unclear. Induction of the antimicrobial peptides cathelicidin (LL37) and human-beta-defensin-2 (HBD-2) may be the mechanism of any benefit. We hypothesised that antimicrobial peptide levels would be decreased, and airway infection and inflammation greater, in CF children with vitamin D deficiency. The objective of the study was to explore relationships between vitamin D, LL37 and HBD-2, and airway infection, inflammation and physiology in children with CF. METHODS: Bronchoalveolar lavage (BALF) and blood were obtained from children undergoing fibreoptic bronchoscopy. Serum vitamin D, BALF HBD-2 and LL37, cultured bacteria and inflammatory markers were measured. Clinical parameters were recorded. RESULTS: 113 patients with CF, 23 with non-CF chronic suppurative lung disease (CSLD) and 6 healthy controls were included. We found no relationship between serum vitamin D and BALF HBD-2 or LL-37. There were no differences in infective or inflammatory markers between vitamin D sufficient and deficient groups. Vitamin D deficient patients (<50 nmol/L) did not have a worse FEV1 (CF: 66 (58-71)% vs. 71.5 (61-76)%, ns; non-CF CSLD: 69 (36-88)% vs. 70 (62-95)%, ns). CONCLUSIONS: In the first bronchoscopic study exploring this question, we demonstrate that vitamin D deficiency is not associated with immunological, infective or clinical markers of disease severity in patients with CF or CSLD.
Hughes D, Archangelidi O, Armstrong-James D, et al., 2018, CLINICAL CHARACTERISTICS OF PSEUDOMONAS AERUGINOSA AND ASPERGILLUS SPECIES CO-INFECTED CYSTIC FIBROSIS PATIENTS IN THE UK, North American Cystic Fibrosis Conference, Publisher: WILEY, Pages: 278-279, ISSN: 8755-6863
Davies JC, Martin I, 2018, New anti-pseudomonal agents for cystic fibrosis- still needed in the era of small molecule CFTR modulators?, EXPERT OPINION ON PHARMACOTHERAPY, Vol: 19, Pages: 1327-1336, ISSN: 1465-6566
Ahmed B, Cox MJ, Cuthbertson L, et al., 2018, Comparison of the upper and lower airway microbiota in children with chronic lung diseases, PLoS ONE, Vol: 13, ISSN: 1932-6203
RationaleThe lower airway microbiota is important in normal immunological development and chronic lung diseases (CLDs). Young children cannot expectorate and because of the uncertainty whether upper airway samples reflect the lower airway microbiota, there have been few longitudinal paediatric studies to date.ObjectivesTo assess whether throat swabs (TS) and cough swabs (CS) are representative of the lower airway microbiota.MethodsTS, CS, bronchoalveolar lavage and bronchial brushings were prospectively collected from 49 children undergoing fibreoptic bronchoscopy for CLDs. Bacterial DNA was extracted and the 16S rRNA gene V4 region sequenced using the Illumina MiSeq.Results5.97 million high quality reads were obtained from 168 samples (47 TS, 37 CS, 42 BALF and 42 bronchial brushings). CS sequenced poorly. At a community level, no difference in alpha diversity (richness, evenness or Shannon Diversity Index) was seen between lower airway samples and TS (P > 0.05). Less than 6.31% of beta diversity variation related to sampling method for TS (P = 0.001). Variation between pathologies and individual patients was greater (20%, 54% respectively P ≤ 0.001) than between TS and lower airway samples. There was strong correlation in the relative abundance of genera between samples (r = 0.78, P < 0.001). Similarity between upper and lower airway samples was observed to be less for individuals where one sample type was dominated by a single organism.ConclusionsAt the community structure level, TS correlate with lower airway samples and distinguish between different CLDs. TS may be a useful sample for the study of the differences in longitudinal changes in the respiratory microbiota between different CLDs. Differences are too great however for TS to be used for clinical decision making.
Bardin EE, Cameron SJS, Perdones-Montero A, et al., 2018, Metabolic phenotyping and strain characterisation of pseudomonas aeruginosa Isolates from cystic fibrosis patients using rapid evaporative ionisation mass spectrometry, Scientific Reports, Vol: 8, ISSN: 2045-2322
Rapid evaporative ionisation mass spectrometry (REIMS) is a novel technique for the real-time analysis of biological material. It works by conducting an electrical current through a sample, causing it to rapidly heat and evaporate, with the analyte containing vapour channelled to a mass spectrometer. It was used to characterise the metabolome of 45 Pseudomonas aeruginosa (P. aeruginosa) isolates from cystic fibrosis (CF) patients and compared to 80 non-CF P. aeruginosa. Phospholipids gave the highest signal intensity; 17 rhamnolipids and 18 quorum sensing molecules were detected, demonstrating that REIMS has potential for the study of virulence-related metabolites. P. aeruginosa isolates obtained from respiratory samples showed a higher diversity, which was attributed to the chronic nature of most respiratory infections. The analytical sensitivity of REIMS allowed the detection of a metabolome that could be used to classify individual P. aeruginosa isolates after repeated culturing with 81% accuracy, and an average 83% concordance with multilocus sequence typing. This study underpins the capacities of REIMS as a tool with clinical applications, such as metabolic phenotyping of the important CF pathogen P. aeruginosa, and highlights the potential of metabolic fingerprinting for fine scale characterisation at a sub-species level.
Rosenfeld M, Wainwright CE, Higgins M, et al., 2018, Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study, Lancet Respiratory Medicine, Vol: 6, Pages: 545-553, ISSN: 2213-2600
BACKGROUND: Ivacaftor is generally safe and effective in patients aged 2 years and older who have cystic fibrosis and specific CFTR mutations. We assessed its use in children aged 12 to <24 months. METHODS: The ARRIVAL study is a phase 3, single-arm, two-part, multicentre study. Eligible children were aged 12 to <24 months at enrolment and had a confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele and could participate in one or both parts of the study. Children received 50 mg (bodyweight 7 to <14 kg) or 75 mg (bodyweight ≥14 to <25 kg) ivacaftor orally every 12 h. In study part A, children received ivacaftor for 3 days plus one morning. In study part B, children received 24 weeks of treatment. Children were enrolled into part A at seven sites in Australia (one site), the UK (one), and the USA (five) and into part B at 13 sites in Australia (two sites), Canada (one), the UK (three), and the USA (seven). Primary endpoints were pharmacokinetics (part A) and safety (parts A and B) in children who received at least one dose of ivacaftor. Secondary endpoints in part B were pharmacokinetics in children who received at least one dose of ivacaftor and absolute change from baseline in sweat chloride concentration. We also explored changes in growth parameters and markers of pancreatic function. This study is registered with ClinicalTrials.gov, number NCT02725567. FINDINGS: Children aged 12 to <24 months were enrolled between Aug 25, 2016, and Nov 1, 2017. Seven children were enrolled in part A, of whom five received 50 mg and two received 75 mg ivacaftor. All completed treatment. Of 19 children enrolled in part B, including one from part A, all received 50 mg ivacaftor and 18 completed treatment (one withdrew because of difficulty with blood draws). All children received at least one dose of ivacaftor. Pharmacokinetics indicated exposure was similar to that in children aged 2 to <6 years and adults. No children discont
Turnbull AR, Murphy R, Behrends V, et al., 2018, Impact of T2R38 receptor polymorphisms on pseudomonas aeruginosa infection in cystic fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 197, Pages: 1635-1638, ISSN: 1073-449X
Edmondson C, Davies JC, 2018, Predicting the future of cystic fibrosis lung disease: gene expression holds some of the answers, Annals of the American Thoracic Society, Vol: 15, Pages: 556-557, ISSN: 2329-6933
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.