Dr Tuomas Jartti
email: tuomas.jartti@utu.fi.

Susanna Kuneinen

Pasi Lehtinen

Ville Peltola

Tytti Vuorinen

Maija Leinonen

Olli Ruuskanen

Nasopharyngeal bacterial colonization during the first wheezing episode is associated with longer duration of hospitalization and higher risk of relapse in young children

Objective: To study the association between bacterial colonization/infection and respiratory outcomes in <3-year-old children hospitalized for their first wheezing episode.

Methods:

This was an observational study. The primary outcome was a hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. 3 physician confirmed wheezing episodes) within 12 months. Bacterial antibody assays for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae, nasopharyngeal bacterial culture for the 3 former and urine pneumococcal antigen were studied.

Results: Nasopharyngeal bacterial culture was positive in 31/52 (60%) children, serologic evidence of bacterial infection was found in 17/96 (18%) children, urine pneumococcal antigen was positive in 24/101 (24%), and any bacterial detection method was positive in 53/106 (50%) children. The children with positive nasopharyngeal bacterial culture had longer duration of hospitalization (hazard ratio 2.4) and more often relapse within two months than those with negative culture (odd's ratio 7.3).

Conclusion:

In this study, a half of the first time wheezing children had bacterial colonization or symptomatic or asymptomatic bacterial infection. The bacterial colonization (i.e. positive nasopharyngeal bacterial culture) was associated with longer duration of hospitalization and higher risk of recurrent wheezing.

Introduction

Acute wheezing illnesses in children are almost exclusively associated with respiratory viral infection [START_REF] Heymann | Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing[END_REF][START_REF] Allander | Human bocavirus and acute wheezing in children[END_REF]. Symptoms are mainly caused by the host immune response to infection, although a direct cytopathic effect of the virus may also contribute [START_REF] Bruder | Cellular immunity and lung injury in respiratory virus infection[END_REF].

Bacterial etiology of acute wheezing has been studied in the past and the negative results as well as no effect from antibiotics have reduced the amount of more recent studies. Evidence of bacteria in the upper airways of children has been found using culture or serology in up to 40% of wheezing children [START_REF] Esposito | Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing[END_REF][START_REF] Normann | Association between Chlamydia pneumoniae antibodies and wheezing in young children and the influence of sex[END_REF][START_REF] Nagayama | Bacterial colonization in respiratory secretions from acute and recurrent wheezing infants and children[END_REF]. These have included Streptococcus pneumoniae (S Pne),

Haemophilus influenzae (H infl), Moraxella catarrhalis (M cat), Mycoplasma pneumoniae (M pne) and Chlamydia pneumoniae (C pne). Approximately a half of wheezing children have had clinical signs of possible bacterial complication (otitis 44%, alveolar infiltrates 10%, or sinusitis 17%); highest numbers (>70%) are for acute otitis media infections in the cases of respiratory syncytial virus induced bronchiolitis [START_REF] Lehtinen | Bacterial coinfections in children with viral wheezing[END_REF].

The reports on the association between bacterial colonization of the airway and severity of illness are scarce. One study found that children with recurrent wheezing and coexistent bacterial colonization and virus infection presented longer duration of hospitalization than those with virus infection but without bacterial colonization [START_REF] Yu | Impact of bacterial colonization on the severity and airway inflammation of children with virus induced wheezing[END_REF]. Interestingly, the risk for recurrent wheezing or asthma has been linked, not only to viral etiology of early wheezing as shown in many studies, but also to bacterial colonization of asymptomatic neonates in one other study [START_REF] Kotaniemi-Syrjänen | Rhinovirus-induced wheezing in infancy--the first sign of childhood asthma?[END_REF][START_REF] Lemanske | Rhinovirus illnesses during infancy predict subsequent childhood wheezing[END_REF][START_REF] Lehtinen | Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema[END_REF][START_REF] Kusel | Earlylife respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma[END_REF][START_REF] Bisgaard | Childhood asthma after bacterial colonization of the airway in neonates[END_REF]. Of the latter, hypopharyngeal colonization with S pne, H infl and/or M cat at age one month has predicted recurrent wheezing and asthma at age 5 years in a birth cohort born to mothers with asthma [START_REF] Bisgaard | Childhood asthma after bacterial colonization of the airway in neonates[END_REF]. Moreover, patients with asthma may be more susceptible to serious pneumococcal disease [START_REF] Talbot | Asthma as a risk factor for invasive pneumococcal disease[END_REF][START_REF] Juhn | Increased risk of serious pneumococcal disease in patients with asthma[END_REF]. The understanding of the significance of bacterial colonization and/or infection in young wheezing children is likely to give clinically relevant information that could help in understanding the risk of recurrent wheezing and in designing early prevention and treatment strategies. Therefore, we studied specific findings of bacterial colonization/infections in less than 3-year-old children hospitalized for their first wheezing episode, and how these findings were associated with the duration of initial hospitalization and occurrence of recurrent wheezing in a 12-month follow-up.

Methods

Subjects

This cross-sectional study is a substudy of the VINKU study which took place in the Department of Pediatrics of Turku University Hospital (9/2000-5/2002). Its original aim was to study the efficacy of oral prednisolone in hospitalized wheezing children in relation to viral etiology, i.e. a half of the patients were randomized to receive oral prednisolon for 3 days and the other half placebo in a double blind design (first dose 2 mg/kg, then 2 mg/kg/d in 3 divided doses). The methods have been described earlier [START_REF] Lehtinen | Bacterial coinfections in children with viral wheezing[END_REF][START_REF] Jartti | The efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus[END_REF][START_REF] Jartti | Efficacy of prednisolone in children hospitalized for recurrent wheezing[END_REF]. The present study included all children of the VINKU study that had their first wheezing episode and age 3 -35 months (Fig. 1). Predefined exclusion criteria were chronic disease (other than asthma or allergy), systemic glucocorticoid treatment within 4 weeks prior to the study, severe wheezing necessitating intensive care unit treatment, and previous participation in this study.

Here, we only included children aged <3 years and experiencing their first wheezing episode since 12 month follow-up data was only available from them. Other children were only followed up to 2 months. The study protocol was approved by the Ethics Committee of the Turku University Hospital and informed consent was obtained from the guardian before commencing the study.

Definitions

Atopy was defined as positive immunoglobulin (Ig) E antibodies to any of the common allergens (cut-off level 0.35 kU/L for codfish, cow's milk, egg, peanut, soybean, wheat, cat, dog, horse, birch, mugwort, timothy, Cladosporium herbarum and Dermatophagoides pteronyssinus; fluoro-enzyme immunoassay, CAP FEIA, Phadiatop Combi ® , Phadia, Uppsala, Sweden). Aeroallergen sensitization was defined as positive IgE antibodies to any of the latter 8 allergens. Perennial aeroallergen sensitization was defined as positive IgE antibodies to dog, cat or Dermatophagoides pteronyssinus. Birch, mugwort, timothy and Cladosporium herbarum were considered as seasonal aeroallergens. Eczema was diagnosed by physician and referred as atopic eczema if any sensitization was present.

Outcome measures

The predefined primary outcome was the time until ready for discharge (hospitalization time), which was defined as a duration of respiratory symptoms score > 3 during the hospital stay. The respiratory symptoms score, which was assessed every 1 2 hours during hospitalization, is a summed score for the degree of dyspnea (0 = none, 1 = mild, 2 = moderate, 3 = severe), type of breathing (0 = normal, 1 = use of stomach muscles, 2 = use of intercostal muscles, 3 = nasal flaring), severity of auscultatory findings on wheezing (0 = none, 1 = expiratory, 2 = inspiratory and expiratory, 3 = audible without stethoscope) and assessment of expiratory:inspiratory time (0 = 1 :2 , 1 = 1 :1 , 2 = 2 :1 , 3 = 3 :1 ). An estimation of 6 hours was used for the last 1 2 -hour period between hospital assessments, i.e. the period during which the patient became ready for discharge. The predefined secondary outcomes were clinic visits for recurrent wheezing during a 2-month period after the discharge for all recruited subjects (n=293) and time to recurrent wheezing (i.e. 3 physician confirmed wheezing episodes) within 12 months after discharge for the first-time wheezing children (n=131) [START_REF] Lehtinen | Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema[END_REF][START_REF] Jartti | The efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus[END_REF][START_REF] Jartti | Efficacy of prednisolone in children hospitalized for recurrent wheezing[END_REF]. In this observational study, we report the associations between specific findings of bacterial colonization/infections and clinical outcomes of the study.

Sample collection and analysis

On admission, a nasopharyngeal aspirate sample was obtained using a standardized procedure, as described previously [START_REF] Jartti | Respiratory picornaviruses and respiratory syncytial virus as causative agents of acute expiratory wheezing in children[END_REF]. Blood samples were collected at study entry and 2-3 weeks later, and analysed as previously described [START_REF] Lehtinen | Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema[END_REF][START_REF] Jartti | The efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus[END_REF][START_REF] Jartti | Efficacy of prednisolone in children hospitalized for recurrent wheezing[END_REF]. Urine samples were collected at study entry. Culture and antigen analyses were done on fresh samples. Otherwise, samples were stored in -70 ºC for later analysis. Bacterial antibody assays to confirm acute S pne, H inf, M cat, M pne and C pne infection were performed on acute and convalescent serum samples as described previously [START_REF] Lehtinen | Bacterial coinfections in children with viral wheezing[END_REF]. Urine pneumococcal antigen and nasopharyngeal bacterial cultures (S pne, H inf, or M cat) were analyzed according to the standard clinical routine of the Central Laboratory, Turku University Hospital, Turku, Finland.

Nasopharyngeal bacterial cultures were added to the protocol in the middle of the study and obtained only from the second study year. Other methods of the study have been previously described [START_REF] Allander | Human bocavirus and acute wheezing in children[END_REF][START_REF] Jartti | The efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus[END_REF][START_REF] Jartti | Efficacy of prednisolone in children hospitalized for recurrent wheezing[END_REF][START_REF] Jartti | Respiratory picornaviruses and respiratory syncytial virus as causative agents of acute expiratory wheezing in children[END_REF].

Statistics

No statistical power calculation was done for this analysis. Kolmogorov-Smirnov test was used to test the normality of data distributions. In the analysis of baseline data, Mann-Whitney U test was used for continuous data since data distributions were skewed, and Chisquare test or Fischer's exact test (when counts <5) were used for categoric data. The outcome data was analysed using Cox or logistic regression analyses. The analyses including bacterial serology were repeated with adjustment to prednisolon treatment due to baseline difference. The statistical analyses were carried out using SPSS/ PC 1 3 .0 software (SPSS Inc, Chicago, IL, USA).

Results

Data set

Of the 293 randomized patients, 131 children fulfilled the criteria for the long-term followup, i.e. the first episode and age 3 -35 months (Fig. 1). Lost to follow-up were 13 children.

Thus, 118 children completed the follow-up. Eleven children (9%) were treated for prolonged cough with a continuous inhaled corticosteroid (by non-study physicians) and were excluded from analyses because of unclear diagnosis. Of the final study cohort (n = 107), 87 children were clinically examined and their parents personally interviewed at 12-month follow-up visit, and the parents of 20 children were interviewed by phone.

Patient characteristics

The median age of the final study cohort was 1.1 years (range 0.3, 2.9). Table 1 shows the characteristics of the study children. Nasopharyngeal bacterial culture (S pne, H inf, or M cat) was positive in 31 of 52 (60%) children, serologic evidence of bacterial infection (S pne, M pne, C pne, H inf, or M cat) was found in 17 of 96 (18%) children, urine pneumococcal antigen was positive in 24 of 101 (24%) children, and evidence of bacterial colonization or infection by any bacterial detection method was found in 53 of the 106 (50%) children (Table 2). Of the 107 children, 100 (93%) had a viral infection. Most common findings were as follows: RSV (46%), rhinovirus (29%), human bocavirus (23%), enteroviruses (16%) and >2 viruses (40/107, 37%). No significant differences were found in patient characteristics between nasopharyngeal bacterial culture + vs. -, bacterial serology + vs. -, or urine pneumococcal antigen detection + vs.groups except that the children who received prednisolone had more often positive bacterial serology (14/47, 30%) than those receiving placebo (3/49, 6%, P = 0.0029) (data shown for nasopharyngeal bacterial culture + vs.groups in Table 3; otherwise data not shown).

Hospitalization Time

The median hospitalization time in children with positive vs. negative nasopharyngeal bacterial culture was 4 8 h (innerquartile range 2 4 , 6 4 ; n = 3 1 ) vs. 1 8 h (1 2 , 2 7 ; n = 2 1 ). The difference was significant (univariable hazard ratio 2 .3 8 ; 9 5 % confidence interval 1 .3 2 , 4 .3 6 ; P = 0 .0 0 4 ) (Fig. 2 A).

Relapse within two months

Children positive for nasopharyngeal bacterial culture were more often readmitted to an outpatient clinic within two months due to recurrent wheezing than those with negative culture. Thirteen of 30 (43%) children with positive nasopharyngeal bacterial culture had a relapse compared to 2 of 21 (10%) children with negative nasopharyngeal bacterial culture (univariable analysis, P = 0.017, Table 4).

Recurrent wheezing within 12 months

Eleven of 3 1 (3 5 % ) children positive for nasopharyngeal bacterial culture and 5 of 2 1

(2 4 % ) children negative for nasopharyngeal bacterial culture had recurrent wheezing within a year (univariable analysis P = 0 .4 9 , Fig. 2 B). Nine of 1 7 (5 3 % ) children positive for bacterial serology and 2 8 of 7 9 (3 5 % ) children negative for bacterial serology had recurrent wheezing within a year (univariable analysis P = 0 .1 1 , multivariable analysis including prednisolon treatment, P = 0 .18, Fig. 2 C). No other significant differencies or tendencies were found.

Discussion

This study showed that bacterial colonization or asymptomatic or symptomatic bacterial infection can be demonstrated in a half of the young children experiencing their first wheezing episode. Moreover, children with positive nasopharyngeal bacterial culture, an indication of bacterial colonization, had a prolonged hospitalization time and more often relapse within 2 months after discharge. Since there were no differences in many baseline characteristics of patients between bacterial culture positive and negative groups, we only used univariate analysis in bacterial colonization data.

Our prevalence numbers for bacterial colonization and infection are comparable to previous studies on normal and wheezing children (4, 6, 19-2 2 ). In wheezing children, [START_REF] Nagayama | Bacterial colonization in respiratory secretions from acute and recurrent wheezing infants and children[END_REF] reported the prevalence of 17% for S pne, H infl and M cat cultured from sputum samples [START_REF] Nagayama | Bacterial colonization in respiratory secretions from acute and recurrent wheezing infants and children[END_REF]. Serologic evidence for M pne infection has ranged from 4% to 23% and for C pne from 3% to 17% in children with acute wheezing [START_REF] Esposito | Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing[END_REF][START_REF] Mertsola | Recurrent wheezy bronchitis and viral respiratory infections[END_REF][START_REF] Ong | Identification of human metapneumovirus and Chlamydophila pneumoniae in children with asthma and wheeze in Singapore[END_REF]. Serologic evidence of H infl and M cat has been <5% in wheezing children [START_REF] Mertsola | Recurrent wheezy bronchitis and viral respiratory infections[END_REF]. The antigenuria for S pne was quite high in our study (24%) in contrast to one previous study (1%) [START_REF] Korppi | Bacterial infection in under school age children with expiratory difficulty[END_REF].

We did not find association to age, but other studies suggest that nasopharyngeal colonization of respiratory bacteria increase after birth and peak during early childhood, and then steadily decrease [START_REF] Nagayama | Bacterial colonization in respiratory secretions from acute and recurrent wheezing infants and children[END_REF][START_REF] Bisgaard | Childhood asthma after bacterial colonization of the airway in neonates[END_REF][START_REF] Watson | Upper respiratory tract bacterial carriage in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia[END_REF][START_REF] Harrison | The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position[END_REF]. Although there is variability in the peak age during childhood between studies, the nasopharyngeal colonization is much less during early adulthood compared to childhood [START_REF] Watson | Upper respiratory tract bacterial carriage in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia[END_REF][START_REF] Cardozo | Prevalence and risk factors for nasopharyngeal carriage of Streptococcus pneumoniae among adolescents[END_REF]. An increase in respiratory bacterial colonization has been associated with low socio-economic status, autumn-winter seasons, exposure to other children, prone sleeping position, upper respiratory or otitis media infection, immunosuppression or lack of immunization, use of pacifiers, hospitalization and xylitol consumption (21, 24, 2 6 ). Allergy has been found to be associated with S pne and H infl carriage in children [START_REF] Borer | Antibiotic-resistant pneumococci carried by young children do not appear to disseminate to adult members of a closed community[END_REF][START_REF] St Sauver | Risk factors for otitis media and carriage of multiple strains of Haemophilus influenzae and Streptococcus pneumoniae[END_REF]. No association or controversial association has been found with gender, diet and parental smoking (5, 6, 1 3 , 21 , 2 4 -2 6 ). Of the factors listed above, we did not find an association between bacterial colonization and atopy, atopic eczema, gender, season, older siblings/day-care, or parental smoking. Children with positive bacterial serology (i.e. indication of symptomatic or asymptomatic infection), however, had more often prednisolone treatment. Although we could not show link between age and bacterial seroconversion, M pne or C pne seroconversion associated wheezing may increase by age [START_REF] Esposito | Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing[END_REF].

Poorer prognosis in children with nasopharyngeal bacterial carriage is in line with one previous study which showed that hypopharyngeal colonization with S pne, H infl, and/or M cat in asymptomatic neonates at 1 month of age was associated with increased risk of a first wheezy episode, persistent wheeze, acute severe exacerbation of wheeze, hospitalization for wheeze, increased blood eosinophil counts and total IgE and, eventually, increased reversibility of airway resistance and development of asthma by the age of 5 years (13).

Interestingly, atopy was not connected with the influence of bacterial findings on prognosiseither in our study nor in the previous study [START_REF] Bisgaard | Childhood asthma after bacterial colonization of the airway in neonates[END_REF]. In another study, the frequency of bacterial colonization in children with recurrent wheezing was higher than that of children with bronchiolitis, which is in line with our results [START_REF] Yu | Impact of bacterial colonization on the severity and airway inflammation of children with virus induced wheezing[END_REF]. Moreover, among the cases with recurrent wheezing, children who had coexisted non-invasive bacterial colonization and virus infection presented more frequent cyanosis, longer duration of hospitalization, higher concentration of IL-10, and higher percentage of neutrophil compared with children with virus infection but without bacterial colonization. In a population-based study on adolescents, pneumococcal colonization was independently associated with a history of an exacerbation of asthma during the preceding year [START_REF] Cardozo | Prevalence and risk factors for nasopharyngeal carriage of Streptococcus pneumoniae among adolescents[END_REF]. The association to allergies was not reported.

The causal direction of the association between nasopharyngeal bacterial colonization and respiratory outcome is unknown: are bacteria triggering susceptible individuals to recurrent wheeze, [START_REF] Bisgaard | Childhood asthma after bacterial colonization of the airway in neonates[END_REF] or are children predisposed to recurrent wheeze more susceptible to bacteria as part of such constitution [START_REF] Talbot | Asthma as a risk factor for invasive pneumococcal disease[END_REF][START_REF] Juhn | Increased risk of serious pneumococcal disease in patients with asthma[END_REF]? Susceptibility to recurrent wheezing is associated with preexisting airway inflammation, altered host defenses and increased risk to bacterial or viral infections or their carriage. Both airway inflammation and decreased resistance for microbes probably predispose for more severe illness and poorer long-term outcome. A normal local immune response to an organism would prevent colonization and limit its duration [START_REF] García-Rodríguez | Dynamics of nasopharyngeal colonization by potential respiratory pathogens[END_REF][START_REF] Faden | Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first 2 years of life[END_REF].

In general, mucosal immunity matures earlier than systemic immunity, and therefore, bacterial colonization pattern may be a first sign of biased immune functions [START_REF] García-Rodríguez | Dynamics of nasopharyngeal colonization by potential respiratory pathogens[END_REF][START_REF] Ghaffar | Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae[END_REF]. These suggestions are supported by studies showing that asthmatics have increased risk for serious pneumococcal infection [START_REF] Talbot | Asthma as a risk factor for invasive pneumococcal disease[END_REF][START_REF] Juhn | Increased risk of serious pneumococcal disease in patients with asthma[END_REF][START_REF] Hartert | Are persons with asthma at increased risk of pneumococcal infections, and can we prevent them?[END_REF]. An inability of asthma prone children to resist bacterial infections may also be comparable to their inability to limit viral infections to the upper respiratory tract [START_REF] Heymann | Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing[END_REF][START_REF] Allander | Human bocavirus and acute wheezing in children[END_REF]. This increased susceptibility to lower respiratory tract viral infections has been shown to relate to defective innate immune responses (3 1 , 3 2 ). Moreover, bacterial and virus infections may have synergistic actions due to the destruction of respiratory epithelium by viral infection which may increase bacterial adhesion, due to the possible virus-induced immunosuppression which may cause more severe bacterial infections, and/or due to the inflammatory response to viral infection which may up-regulate expression of molecules that bacteria utilize as receptors [START_REF] Peltola | Respiratory viruses predisposing to bacterial infections: role of neuramidase[END_REF]. We, however, speculate that bacterial colonization is probably just a "by-stander" factor since it was not linked to most distant outcome, recurrent wheezing, in our study. Antibiotic treatment did not influence the prognosis in our study. This is in line with general consideration that antibiotics do not effectively eradicate bacterial colonization from the nasopharynx (2 1 ). The reduction in carriage is considered only temporary. Antibiotics induce suppression of susceptible bacteria, but after antibiotic treatment, a rapid replacement of strains usually occurs with either overgrowth of more resistant strains that were masked by other organisms or by newly acquired resistant strains. Although our study was not properly designed to answer the effect of antibiotic treatment (antibiotic use was decided on clinical bases), our results are in agreement with [START_REF] Kusel | Antibiotic use in the first year of life and risk of atopic disease in early childhood[END_REF], who did not find association between the receipt of antibiotics in the first year of life and subsequent development of atopy, current wheeze or asthma at age 5 years [START_REF] Kusel | Antibiotic use in the first year of life and risk of atopic disease in early childhood[END_REF]. Overall, prognosis being independent of antibiotic treatment further supports the hypothesis that bacteria in predisposed children are most likely just by-standers indicating high risk individuals. Possible interventions should not primarily be directed against the microbe, instead they should be designed to reduce the underlying inflammatory condition predisposing to an infection or colonization. Interestingly, our finding of increased prevalence of bacterial seropositivity in the prednisolone group raises naturally a question whether systemic corticosteroids even with therapeutic doses could increase the risk of bacterial infections. However, short courses of systemic corticosteroids have been found safe in the treatment of childhood wheezing [START_REF] Jartti | Systemic glucocorticoids in childhood expiratory wheezing: relation between age and viral etiology with efficacy[END_REF].

Our study has some limitations. Since nasopharyngeal bacterial colonization increases significantly during acute respiratory infections, we can not differentiate bacterial colonization from asymptomatic or symptomatic bacterial infection in our study (2 1 ).

However, positive findings in nasopharyngeal bacterial culture or urine pneumococcal antigen detection are usually considered as an indication of bacterial colonization, and seroconversion as an indication of symptomatic or asymptomatic infection. Isolation of a potential bacterial pathogen from upper respiratory secretions does not exactly reflect infection of the lower airways. Instead, bronchoalveolar lavage sampling is considered as the most optimum methods for lower airway colonization since it is believed to be sterile. In agreement with our findings, bacteria and increased numbers of inflammatory cells have been reported in bronchoalveolar lavage fluid in wheezing and asthmatic children [START_REF] Marguet | Bronchoalveolar cell profiles in children with asthma infantile wheeze, chronic cough, or cystic fibrosis[END_REF][START_REF] Fayon | Bacterial flora of the lower respiratory tract in children with bronchial asthma[END_REF][START_REF] Krawiec | Persistent wheezing in very young children is associated with lower respiratory inflammation[END_REF][START_REF] Bourgeois | Bronchoalveolar cells in children < 3 years old with severe recurrent wheezing[END_REF]. The follow-up period was limited to 12-months, and data were only available from children experiencing their first wheezing episode. Nasopharyngeal bacterial cultures where obtained only from the second study year which explains their low number. Comparisons were done within wheezing children and there was no healthy control group. Sample size was rather small, and no statistical power analysis was not done since this was a post hoc analysis.

In conclusions, bacterial colonization and/or infection was found in a half of the children with acute wheezing in this study. Most importantly, the bacterial colonization was associated with prolonged hospitalization and increased risk of relapse, which is a new finding. Since the prevalences of traditional risk factors of recurrent wheeze/asthma in young children, any sensitization and especially aeroallergen sensitization, are low during infancy, new risk markers are needed [START_REF] Illi | Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study[END_REF][START_REF] Jartti | Bronchiolitis: age and previous wheezing episodes are linked to viral etiology and atopic characteristics[END_REF]. Nasopharyngeal bacterial colonization could serve as a new and early marker for those at an increased risk for a relapse. This data provides preliminary evidence for doing a larger prospective study. Univariable regression analysis. 1 The numbers for those completing the 2-month follow-up.

Legends to the figures

Figure 1 .

 1 Figure 1. Study flow chart.

Figure 2 .

 2 Figure 2. A. The Kaplan-Meier plot of the hospitalization time in the first-time wheezing children with positive (bolded line) and negative nasopharyngeal bacterial culture (dashed line). Univariable hazard ratio 2.38; 95% confidence interval 1.32, 4.36. B. Time to recurrent wheezing (i.e. 3 physician confirmed wheezing episodes) within 12 months in the first-time wheezing children with positive (bolded line) and negative nasopharyngeal bacterial culture (dashed line). Univariable hazard ratio 1.46; 95% confidence interval 0.50, 4.28. C. Time to recurrent wheezing within 12 months in the first-time wheezing children with positive (bolded line) and negative bacterial serology (dashed line). Univariable hazard ratio 1.86; 95% confidence interval 0.88, 3.95. See text for details.

Table 2 .

 2 Bacterial findings.

	Bacterial detection positive	n (%)
	Any nasopharyngeal bacterial culture	31/52 (60%)
	Streptococcus pneumoniae	13/52 (25%)
	Haemophilus influenzae	11/52 (21%)
	Moraxella catarrhalis	16/52 (31%)
	Any bacterial serology	17/96 (18%)
	Chlamydia pneumoniae	2/97 (2%)
	Mycoplasma pneumoniae	5/101 (5%)
	Streptococcus pneumoniae	7/97 (7%)
	Haemophilus influenzae	3/97 (3%)
	Moraxella catarrhalis	2/97 (2%)
	Urine pneumococcal antigen	24/101 (24%)
	Any bacterial detection method (>1 method done) 53/106 (50%)
	Streptococcus pneumoniae	31/106 (29%)
	Haemophilus influenzae	13/101 (13%)
	Moraxella catarrhalis	17/100 (17%)

Table 3 .

 3 Patient characteristics in children with positive and negative nasopharyngeal bacterial culture.

	Factor	Nasopharyngeal bacterial culture	P
		Positive	Negative
		n = 31	n = 21
	Age, years	1.1 (0.5; 1.5)	0.8 (0.5; 2.0)	0.73
	Male gender	18 (58%)	15 (71%)	0.33
	Prematurity	5 (16%)	4 (19%)	1.00
	Eczema	11 (35%)	7 (33%)	0.87
	Atopic eczema, No (%)	3 (9.7%)	1 (4.8%)	0.51
	Atopy, No (%)	4 (13%)	2 (9.5%)	0.71
	Food sensitization, No (%)	4 (13%)	2 (9.5%)	0.71
	Aeroallergen sensitization, No (%)	2 (6.5%)	0 (0.0%)	0.24
	Perennial, No (%)	1 (3.2%)	0 (0.0%)	0.41
	Seasonal, No (%)	2 (6.5%)	0 (0.0%)	0.24
	B-Eos, x 10 9 /L	0.1 (0.0; 0.2)	0.1 (0.1; 0.2)	0.24
	B-Eos ≥0.4 x 10 9 /L	4 (13%)	2 (9.5%)	0.71
	Rhinovirus, No	7 (23%)	4 (19%)	1.00
	Respirtory syncytial virus, No	22 (71%)	13 (62%)	0.56
	Enterovirus, No	4/29 (14%)	4 (19%)	0.71
	Bocavirus, No	5/27 (19%)	3 (14%)	1.00
	Mixed viral infection, No.	13 (42%)	8 (38%)	0.78
	Exhaled nitric oxide, ppb	5.0 (3.8; 8.2)	5.2 (4.0; 7.5)	0.81
	Parental asthma, No (%)	5 (16%)	5 (24%)	0.49
	Parental allergy, No (%)	19 (61%)	12 (57%)	0.76
	Parental smoking, No (%)	16 (52%)	10 (48%)	0.78
	Older sibling or day care, No (%)	28 (90%)	18 (86%)	0.61
	Antibiotic treatment, No (%)	24 (77%)	16 (76%)	0.92
	Acute otitis media, No (%)	20 (65%)	14 (67%)	0.87
	Oral prednisolon, No.	15 (48%)	11 (52%)	0.78
	B-Eos, blood eosinophils; ppb, parts per billion.

Values are shown as medians (interquartile range) or number (%).

Mann-Whitney U test, Chi-square test, or Fischer's exact test were used when appropriate.

Table 4 .

 4 Associations between bacterial finding and clinic visits due to a relapse within two months after hospitalization.

	Bacterial detection positive	n 1	Odds ratio	95% CI	P
	Nasopharyngeal bacterial culture	51	7.27	1.43, 36.94 0.017
	Bacterial serology	90	1.39	0.39, 4.99	0.62
	Urine pneumococcal antigen	92	0.93	0.32, 2.71	0.89
	Any bacterial detection method	97	2.30	0.91, 5.86	0.080
	CI, confidence interval.

Supported by the Academy of Finland (Grants 114034 and 132595), the Finnish Cultural Foundation, the Turku University Foundation, the Foundation for Pediatric Research, the Foundation for Out-patient Research, and the Paulo Foundation.

Conflict of interest: none.

Legends to the figures


Xin Tu

Helen J Gallon

Martyn V Twigg

Peter A Gorry

J Christopher Whitehead
email: j.c.whitehead@manchester.ac.uk

Prof J Christopher

Dry reforming of methane over a Ni/Al 2 O 3 catalyst in a coaxial dielectric barrier discharge reactor

Keywords: Dielectric barrier discharge, Plasma-catalysis, Breakdown, Dry reforming, Hydrogen production PACS: 52.80.-s, 52.40.Hf, 88.30.-k, 82.33.Xj

A coaxial double dielectric barrier discharge (DBD) reactor has been developed for plasmacatalytic conversion of CH 4 and CO 2 into syngas and other valuable products. A supported metal catalyst (Ni/Al 2 O 3 ) reduced in a methane discharge is fully packed into the discharge region. The influence of the Ni/Al 2 O 3 catalyst packed into the gas gap on the electrical characteristics of the discharge has been investigated. The introduction of the catalyst pellets leads to a transition in discharge behaviour from a typical filamentary microdischarge to a combination of spatially-limited microdischarges and a predominant surface discharge on the catalyst surface. It is also found that the breakdown voltage of the CH 4 /CO 2 discharge significantly decreases when the reduced catalyst is fully packed in the discharge area.

Conductive Ni active sites dispersed on the catalyst surface contribute to the expansion of the discharge and enhancement of charge transfer. In addition, plasma-catalytic dry reforming of CH 4 has been carried out with the reduced Ni/Al 2 O 3 catalyst using a mixing ratio of CH 4 /CO 2 = 1 and a total flow rate of 50 ml min -1 . An increase in H 2 selectivity is observed compared to dry CH 4 reforming with no catalyst, while the H 2 /CO molar ratio greatly increases from 0.84 to 2.53 when the catalyst is present.

Introduction

Currently, the demand for effective renewable, alternative energy sources is becoming ever more urgent. The conversion and utilization of abundant low value gases like methane in the form of biogas or landfill gas for the production of fuels and value-added chemicals have exhibited promising potential. The reforming of methane with carbon dioxide, also known as dry reforming, has recently attracted considerable interest due to simultaneous utilization and reduction of two major greenhouse gases, CH 4 and CO 2 .

CH 4 + CO 2 2CO + 2H 2 H°= 247 kJ mol -1 (1)
where H°is the standard enthalpy. This process generates synthesis gas (syngas) with a low H 2 /CO ratio, which is preferred for the synthesis of valuable oxygenated chemicals and long-chain hydrocarbons. Nevertheless, dry reforming of methane using conventional catalytic methods still faces two major challenges that limit the use of this process on a commercial scale: firstly, high operating temperatures (> 700 o C) are required to obtain reasonable yields of syngas due to the very endothermic reaction (1) and the strength of the C-H bonds in methane, incurring high energy cost; secondly, the formation of severe coke deposition and a subsequent blocking of active metal sites on the catalyst surface, causing rapid deactivation of the catalysts, especially for non-noble metal catalysts [1].

Non-thermal plasma is considered as an attractive alternative for converting greenhouse gases into syngas and other valuable chemicals at lower temperature. Highly reactive species generated in such plasma are favorable for both the initiation and propagation of chemical reactions. Non-thermal plasma has a non-equilibrium characteristic due to a significant difference in temperature between the electrons and heavy particles (ions, atoms, free radicals and excited species). The highly energetic electrons can reach an energy of 1-10 eV, while the gas kinetic temperature of the plasma can be as low as room temperature, which enables reactions thermodynamically unfavoured to occur at low temperature [2][3]. Several different types of plasma have been investigated for dry reforming of CH 4 over the past decade, most notably, dielectric barrier discharge [4]- [6], atmospheric plasma jet [7], gliding arc [8] and corona discharge [9] [10]. Whilst the use of a plasma discharge alone has shown that syngas can be generated at low temperature and atmospheric pressure, the selectivities towards the desired products are typically low. In addition to syngas, significant amounts of higher hydrocarbons (C 2 -C 4 ), oxygenates, liquid hydrocarbons and polymers can be formed [4] [11].

Recently, the combination of plasma and heterogeneous catalysis for fuel production from hydrocarbon reforming has attracted increasing interest [11]- [16]. The interaction of plasma with catalyst could generate a synergistic effect, which might provide a unique way to separate the activation steps from the selective reactions [17]- [22]. Up until now, most of these studies mainly focus on the plasma-catalytic chemical reactions to maximize the process performance [11]- [16], while the interaction mechanisms involved in the combination of plasma with catalyst have received less attention from both physical and chemical perspectives [23]- [START_REF] Tu | 12 th Int. Symp. High Pressure Low Temp. Plasma Chem[END_REF]. The interactions between plasma and catalyst become complex when the catalyst is placed directly in the plasma discharge. Both the chemical and physical properties of the plasma and catalyst can be modified by the presence of each other. Therefore, a better understanding of the plasma-catalyst interactions is required from both a scientific and engineering point of view.

In this paper, we report experimental results on dry reforming of methane in a coaxial ). A LABVIEW system is used for the online real-time measurement of discharge power by the area calculation of Q-U Lissajous figure [START_REF] Manley | [END_REF]. Images of the discharge are recorded using a high-speed digital camera (Vision Research, Phantom v710). A trap cooled by solid CO 2 is placed at the exit of the plasma reactor in order to condense any liquid products. The feed and product gases are analyzed by a two-channel micro gas chromatography (Agilent 3000A) equipped with two thermal conductivity detections (TCD).

The first channel contains a Molecular Sieve 5A column for the separation of H 2 , CO and CH 4 , while the second channel is equipped with a Poraplot Q column for the measurement of CO 2 and C 2 -C 4 hydrocarbons. The GC has been calibrated for a wide range of concentrations for each gaseous component by using reference gas mixtures (Agilent Universal Gas Mixture) from Agilent and other calibrated gas mixes.

Calculation of parameters

Figure 2 shows an equivalent electrical circuit of the DBD reactor. This model consists of two capacitors in a series connection. One of the capacitors C d represents the total series capacitance of both dielectric quartz tubes and the other is the capacitance for the gap C g . In the presence of the solid catalyst in the gas gap, C g represents the contribution of the gas-solid integration in the inter-electrode region. In our study, the equivalent capacitance of the dielectric C d is 36.2 pF, which is calculated using the coaxial topology of a double quartz barrier [27]. When the plasma is generated, a resistive channel appears in parallel to C g . The switch 'K' on the equivalent electrical circuit is fictional.

Figure 3 shows a typical Q-U Lissajous figure for a DBD. Lines BC and DA represent the discharge-off phase when there is only displacement current. The slope of the lines BC and DA corresponds to C cell in the plasma-off period, which is formed by the dielectric capacitance C d and the capacitance of the gap C g . The value of C cell can be expressed as

cell d g 1 1 1 C C C = + (1)
Thus, the capacitance of the gap C g in the discharge-off phase can be calculated as follows:

d cell g d cell C C C C C × = - (2)
In the Lissajous figure, lines AB and CD represent the discharge-on phase when the gas breakdown occurs in the gap and plasma is ignited. The slope of these lines is the effective capacitance C eff and should be equal to C d for a fully bridged gap [28].

The charge Q flowing through the DBD cell can be measured from the voltage drop U c across an external capacitance C ext (22 nF) according to the relation

Q = C ext × U c . (3)
The voltage on the dielectric material U d can be obtained from the following equation [29]:

ext c d d d C U Q U C C × = = . (4)
Thus the gas voltage U g across the gap can be given as:

g a d U U U = - (5)
The breakdown voltage, U B is the voltage across the gap at which plasma is ignited. U B can be calculated from the following equation [30][31]

B min g d 1 U U C 1 C = + (6)
The peak to peak charge (Q pk-pk ), charge discharged (Q d ) and charge transferred per half cycle (Q trans ) are also taken from a measurement of the Lissajous figure as plotted in Figure 3 [29].

For the dry reforming reaction, the conversion rates of CH 4 and CO 2 are defined as

4 4 CH 4 moles of CH converted C (%) 100 moles of CH input = × (7) 2 2 CO 2 moles of CO converted C (%) 100 moles of CO input = × (8)
The selectivity of the products can be calculated as

x y

x y C H 4 2

x moles of C H produced S (%) 100 moles of CH converted moles of CO converted

× = × + (11) 4 2 2 CH H H C S Y (%) 100 × = (12)
The H 2 /CO molar ratio and carbon balance are defined as follows:

2 2 H moles of H produced CO moles of CO produced = ( 13
) 4 out 2 out out 2 out 3 out Carbon 4 in 2 in [CH ] [CO ] [CO] 2 [C ] 3 [C ] B (%) 100 [CH ]
[CO ]

+ + + × + × = × + (14)
The energy efficiency of a plasma reactor for gas conversion is defined as the number of moles of gas converted per unit of plasma power: We can see the discharges generated between the pellet and quartz wall are much brighter compared to those formed between the pellets. The distance between two pellets or the pellet-quartz wall around their contact points is of primary importance for the generation of filaments. Meanwhile, packing the catalyst pellets into the gas gap introduces a packed-bed discharge effect [18][19], which is characterized by a significant surface discharge on the surface of the packing material. In our case, surface discharges are generated and spread over the surface of the catalyst pellets due to the packed-bed effect. We can see corona-like discharge around the catalyst surface and the luminance intensity of the surface discharges is much weaker than that of the filamentary discharges generated between the pellet and quartz wall (Figure 5). Our previous studies have shown that increasing discharge power or applied voltage could lead to the expansion of the microdischarge channels transforming into surface discharges in a BaTiO 3 packed bed DBD reactor [34]. Thus, the discharge with fully packed catalyst is a combination of surface discharge on the surface of the catalyst pellets and spatially-limited microdischarges generated in the void space between the pellets and the pellet-quartz wall. The relative contribution of filamentary and surface discharges is likely to depend on many factors including particle size, particle shape and packing location, and hence volume fraction of the packed material in the discharge area. In Figure 5, we can see the spatial distribution of the discharge in the presence of the Ni/Al 2 O 3 catalyst is much wider than that of the discharge packed with Al 2 O 3 . This phenomenon suggests that the conductive Ni active sites on the catalyst also contribute to the spread and expansion of the discharge over the pellet surface. Kim and co-workers have also reported that zeolite-supported metal catalysts assisted the expansion of the discharge over the catalyst surface in a packed bed DBD reactor [24].

In Figure 4, we can also see that the gas voltage of the discharge with catalyst is much lower than that of the discharge without packing. It is worth noting that the breakdown voltage (U B ) decreases significantly with the addition of reduced catalyst from 3.3 to 0.75 kV.

This phenomenon can be demonstrated experimentally in that the discharge is much easier to ignite when the reduced catalyst is presented in the plasma reactor. Similar discharge transition behaviour has also been found in our previous studies [START_REF] Tu | 12 th Int. Symp. High Pressure Low Temp. Plasma Chem[END_REF] where the breakdown voltage for a N 2 DBD packed with zeolite 3A is much lower (1.4 kV) than that for the discharge when no packing material is present (2.3 kV). Guaitella et al have also reported a slight decrease in the breakdown voltage of an air-C 2 H 2 discharge when a porous material (<1 mm thick) containing TiO 2 nanoparticles ( r =110) was placed on the inner surface of the dielectric quartz tube in a coaxial DBD reactor [23]. They suggested that the decrease of the breakdown voltage is mainly due to charge deposited on the dielectric surface and the gas phase modification. Cho et al. have compared the breakdown voltage of discharges using different dielectric barriers in a coaxial DBD reactor [35]. They found that the breakdown voltage between the porous alumina surfaces is only half of the voltage for the discharge between smooth polyimide films even though these two materials have a similar dielectric constant (4.5 for porous alumina and 3.5 for Kapton polyimide film). Large difference in breakdown voltage is ascribed to the transition of the discharge behaviour [35]. In our experiment, the total gas flow rate is kept constant. The size of the catalyst pellets are chosen to be large enough to avoid any pressure drop when packing the catalyst in the DBD reactor.

The dielectric constant of the supported metal catalyst (Ni/Al 2 O 3 ) is roughly estimated to be about 50 [36]. Previous observation of a reduction in the breakdown voltage in a nitrogen DBD using different packing materials (Al 2 O 3 , TiO 2 , zeolite 3A) suggests that the influence of gas composition or dielectric constant in the range of r < 100 may have played a very minor role on the decrease of the breakdown voltage in our experiment [START_REF] Tu | 12 th Int. Symp. High Pressure Low Temp. Plasma Chem[END_REF]. In our study, we believe that this effect can be attributed to a change in discharge mode in going from typical filamentary discharge to a combination of weak filamentary and predominantly surface discharge when the reduced catalyst is used. An effective decrease of the breakdown voltage can be reached in the surface discharge [START_REF] Fridman | Plasma Chemistry[END_REF]. Thus the breakdown of gas in the formation of surface discharge is likely to require a lower breakdown voltage due to the accumulation of charges that occur on the surface of the packing material. The presence of the catalyst pellets in the discharge zone also leads to a significant non-uniformity of the electric field and local overvoltage, especially around the contact points between pellet-pellet and pellet-quartz wall.

The amplitude spectra of the current signals are obtained by means of fast Fourier transform (FFT), as plotted in Figure 6. One prominent peak of 35 kHz is clearly visible in both spectra. This peak originates from the excitation frequency of the high voltage transformer and is independent of any change of the gas flow rate, discharge power and packing material. In addition, another group at around 100 MHz can also be found in the FFT spectra for discharge with and without packing. This frequency is power independent and can be attributed to the lifetime of a single microdischarge (~10 ns) in the discharge. The amplitude of this frequency in both spectra is very low. For the discharge with the Ni catalyst, a broad peak at around 12 MHz can be observed, which is directly related to the appearance of a current cluster with duration of 70 -90 ns in the discharge (Figure 4). However, no prominent peak can be observed for the current clusters in the discharge without packing.

Lissajous figures of the discharge with and without packing material are shown in Figure 7 for a constant discharge power of 50 W. We can see that the shape of the Lissajous figure for the discharge changes from a parallelogram to oval shape when the reduced Ni/Al 2 O 3 catalyst is packed in the plasma reactor. This further indicates that physical changes to the discharge mode have taken place. The results in Figure 4 show that despite the constant dissipated power in the plasma discharge, the applied voltage increases from 16.5 kV pk-pk , in the case of no packing to 18.8 kV pk-pk with the Ni/Al 2 O 3 catalyst. Given that the discharge power is the same in each case, the current must be smaller in the catalyst-packed plasma discharges, which can be confirmed from the electrical signals of the discharge (Figure 4).

In the discharge-off phase (lines DA and CB), the total equivalent capacitance of the DBD, C cell , without catalyst is about 7.5 pF, which is independent of the discharge power. This value is also consistent with the capacitance of the DBD cell (7.1 pF) as measured by using a capacitance meter (RS, MEGGER). We can see that this value increases to ~18.5 pF when the DBD reactor is packed with the Ni/Al 2 O 3 catalyst. In the discharge-off phase, the gap capacitance also increases from 9.5 to 37.5 pF when the catalyst pellets are fully packed into the electrode gap. capacitance C eff should be equal to C d for a fully bridged gap [28]. In our study, the C eff is much lower than the capacitance of dielectric quartz tubes (C d =36.2 pF) and is power dependent, especially for the plasma without packing. In the absence of the catalyst, we have observed that the microdischarges do not completely cover the dielectric surface in the gap at the discharge power between 20 W and 60 W due to large gap distance and low power density.

The discharge extends across the gas gap with the increase of the discharge power. In addition, these phenomena also suggest that the C eff depends on the spatial distribution of the discharge across the gap over a half-period of the applied voltage. When the Ni/Al 2 O 3 catalyst pellets are packed into the gap, we can note that the effective capacitance increases compared to that for the discharge without packing. In our work, packing catalyst into the gap leads to a formation of spatially limited filamentary discharges in the void between the pellets and the pellet-quartz wall. The increase of the C eff in the combination of plasma and catalyst can also demonstrate the presence of the surface discharge in a large area of the gap since the catalyst is fully packed into the gap and the surface discharge can be widely distributed. In addition, we find that the C eff for the discharge with just Al 2 O 3 packing (25.8 pF) is much lower than that for the discharge with the Ni/Al 2 O 3 packing (33.5 pF). This comparison further demonstrates that packing the reduced Ni catalyst into a DBD reactor leads to spatial expansion of the discharge across the gap.

Figure 9 shows the influence of the Ni/Al 2 O 3 catalyst on the charge generation and transfer in the discharge at different power levels. It can be clearly seen that the peak to peak charge greatly increases with the increase of the discharge power even at a constant applied voltage (16.5 kV) for the discharge without catalyst. Both the charges generated and transferred per half cycle of the applied voltage also increase with plasma power. It is interesting to note that packing the Ni/Al 2 O 3 catalyst into the discharge gap significantly enhances the peak to peak charge and charge generated per half cycle, which suggests that there is a significant effect of the catalyst on the charge characteristics of the DBD. In addition, we can see that the transferred charge per half cycle for the plasma with catalyst increases by about 10 % in comparison to that for the discharge without packing. It is worth noting that using metal oxide materials (e.g. Al 2 O 3 ) or unreduced NiO/Al 2 O 3 catalyst in the discharge region decreases the transferred charge per half cycle, which means that non-conductive packing materials in the discharge could inhibit the charge transfer between the electrodes [40]. However, the presence of the conductive Ni active sites on the catalyst surface acts as a bridge between the electrodes and promotes charge transfer in the discharge due to the increase of charge carrier production and mobility [36]. Moreover, charge is deposited on the gas gap due to the presence of the catalyst. This can also be demonstrated by a larger capacitance value (C g ) of 37.5 pF in the gap, about four times the magnitude of the capacitance with no packing (9.5 pF).

Plasma-catalytic dry reforming reaction

Plasma-catalytic dry reforming of CH 4 has been carried out with a plasma-reduced Ni/Al 2 O 3 catalyst using a mixing ratio of CH 4 /CO 2 = 1 and a total flow rate of 50 ml min -1 . H 2 and CO are the major reaction products, while smaller amounts of acetylene, ethylene, ethane and propane are also formed. Conversions of both CH 4 and CO 2 increase with increasing plasma power as shown in Figure 10. The conversion rate of CH 4 and CO 2 increases up to 18 and 13 %, respectively, at a discharge power of 100 W. Previous modelling and experimental studies have shown that increasing plasma power at a constant excitation frequency effectively enhances the electric field, electron density and gas temperature in the discharge [START_REF] Tu | 12 th Int. Symp. High Pressure Low Temp. Plasma Chem[END_REF][41] [42]; all of which may contribute in different ways to the improvement in conversion for both gases. In addition, an increase of power produces more active species, such as O and OH, and can also dissociate CH 4 producing more methyl radicals. With the present plasma-catalyst interaction configuration, the maximum energy efficiency, E, for CH 4 and CO 2 conversion, equaling 0.033 mmol kJ -1 (equation [START_REF] Song | [END_REF], is achieved at a discharge power of 97 W and a total flow rate of 50 ml min -1 . At a higher flow rate, the conversion efficiency can be improved though the conversion rate will be lower. Further improvement of the energy efficiency in DBDs is to be expected from the optimization of the catalyst packing, catalyst activity and reactor geometry. Our recent work has shown that the energy efficiency for plasma-catalytic dry reforming can be increased by a factor of 8 (0.23 mmol kJ -1 ) when Ni catalyst pellet was axially packed along a gap (3 mm in gap width) and activated by an argon-hydrogen plasma [START_REF] Tu | 8 th Technological Plasma Workshop[END_REF]. In addition, the energy efficiency of a plasma reactor could be enhanced by a factor of 4 when using rectangular pulses instead of a sinusoidal voltage [START_REF] Martens | [END_REF].

At discharge powers between 70 and 100 W, the selectivity towards H 2 increases steadily from 35 to 45 % (Figure 11). This result is greater than the H 2 selectivities obtained in the absence of the catalyst or with any of non-conductive packing materials [40]. The CO selectivities are in the range 18 -25 % for discharge powers between 70 and 100 W. The selectivities towards CO are much lower than those observed in the absence of a catalyst and for the use of other packing materials, which are in the range 24 -37 % at a discharge power of 35 W. These results are in contrast to results obtained by Song et al. [START_REF] Song | [END_REF], who found that the H 2 selectivity decreased slightly and the CO selectivity increased when a Ni/Al 2 O 3 catalyst was used during dry reforming of methane at a discharge power of 130 W. In addition, it can be noted that the selectivity of higher hydrocarbon products decreases as plasma power is increased. The maximum C 2 selectivity of 12.4 % can be achieved at a discharge power of 70 W. This suggests that an increase in plasma power leads to a change in the reaction pathways and thus changes the product distribution by converting higher hydrocarbons into more hydrogen. As shown in Figure 12 lead us to suggest that the physical and chemical interactions between plasma and catalyst may be responsible for the inverse effect of the plasma-catalysis method. Previous studies have also demonstrated that a synergistic effect due to the interaction of plasma and catalyst cannot be generalized to all plasma-catalytic reactions. We believe that the synergistic effect of the combination of plasma with catalysis for hydrocarbon reforming depends on the balance between the change in discharge behavior induced by the catalyst and the plasma-generated activity of the catalyst. Packing catalyst pellets into the discharge area has been found to shift the discharge behavior from microdischarge in the gas to a combination of surface discharge and weak microdischarges. The relative contribution of filamentary and surface discharges is likely to depend on the volume fraction of the packed material in the discharge area. Such a transition in behaviour of the discharge could reduce the conversions of methane and carbon dioxide, hence the conversion energy efficiency. If the generated surface discharge can increase the activity of the catalyst, the decrease of conversion due to the decrease of discharge current and reduced microdischarges could be compensated for by an improvement in conversion induced by a catalytic effect. However, a strong catalytic effect in the plasma dry reforming reactions could be inhibited or even disappear due to a decrease of catalyst activity or if the catalyst is deactivated by carbon deposition. In this case, the decrease of the conversion by the transition of the discharge behavior cannot be compensated by a catalytic effect, which leads to an overall decrease of the conversion and energy efficiency in the plasma-catalytic process.

Conclusion

In this study, plasma-assisted catalysis dry reforming of methane has been investigated using

Figure 1

 1 Figure 1(a) shows a schematic diagram of the experimental setup. The experiment is

1

 1 Figure 4 presents electrical signals of the discharge in the mixing of CH 4 and CO 2 with and

Figure 8

 8 Figure8shows the effect of packing catalyst on the effective capacitance of the dielectric

a

  DBD reactor combined with a plasma reduced Ni/Al 2 O 3 catalyst. The introduction of the reduced Ni/Al 2 O 3 catalyst into the plasma region significantly changes the physical characteristics of the CH 4 /CO 2 discharge compared to that in the absence of the catalyst.The CH 4 /CO 2 DBD with no catalyst can be characterized as a typical filamentary discharge, while the discharge with fully packed catalyst is a combination of surface discharges on the catalyst surface and spatially-limited microdischarges generated in the gas-filled space between the pellets and the pellet-quartz wall. The relative contribution of filamentary and surface discharges is likely to depend on many factors including particle size, shape and their location, and hence the volume fraction of the packed material in the discharge area. It is found that the presence of the reduced Ni/Al 2 O 3 catalyst in the discharge greatly decreases the breakdown voltage due to a significant enhancement of local electric field and increased charge deposition on the catalyst surface. We have also shown that conductive Ni active sites dispersed on the catalyst surface contribute to the expansion of discharges and enhancement of charge transfer in the discharge. In addition, we find the presence of the Ni/Al 2 O 3 catalyst leads to a decrease in conversions of CH 4 and CO 2 and an increase of H 2 selectivity in comparison with plasma dry reforming in the absence of a catalyst. We have proposed that this effect of plasma-catalyst interaction for reforming reactions can be explained by the balance between the transition in discharge behaviour induced by the catalyst and the durability of the catalyst activity during the plasma catalysis reactions.AcknowledgementSupport of this work by SUPERGEN XIV -Delivery of Sustainable Hydrogen part of the Energy Programme), the Joule Centre and from the UK EPSRC Engineering Instrument Pool is gratefully acknowledged. The Energy Programme is an RCUK cross-council initiative led by EPSRC and contributed to by ESRC, NERC, BBSRC and STFC.

Figure 1 .Figure 2 .Figure 3 .Figure 4 .Figure 5 .

 12345 Figure 1. (a) Schematic diagram of the experimental setup; (b) High voltage power supply

Figure 6 .Figure 7 .Figure 8 .Figure 9 .Figure 10 .Figure 11 .Figure 12 .Figure 13 .Figure 1

 6789101112131 Figure 6. FFT spectra of current signals in the discharge (a) without packing; (b) with reduced

Figure 3

 3 Figure 3

Figure 4

 4 Figure 4(a)

Figure 6

 6 Figure 6(a)

Figure 8

 8 Figure 8

Figure 9

 9 Figure 9(a)

Figure 11

 11 Figure 11

Figure 12

 12 Figure 12

Figure 13

 13 Figure 13

  , the highest yield of H 2 (8.2 %) is obtained for the CH 4 plasma-reduced Ni/Al 2 O 3 catalyst, at a discharge power of 97 W.The carbon balance in the gas stream for the use of catalyst is over 90%. Higher conversions of CH 4 and CO 2 at increased discharge powers are accompanied by higher carbon deposition. As previously described, carbon deposition could be a result of several reactions including methane decomposition, the Boudouard reaction and possibly electron impact dissociation of other carbonaceous molecules that might produce solid carbon. The formation of H 2 as a percentage of the total gas mixture resembles a mirror image of the carbon balance.Following this observation, it is suggested that methane decomposition to give solid carbon and H 2 is the dominant process that is responsible for carbon deposition during these experiments. The H 2 /CO ratio is changed significantly by increased H 2 selectivity and constant CO selectivity. The presence of the reduced Ni/Al 2 O 3 catalyst increases the H 2 /CO ratio from 0.84 to 2.53 as shown in Figure13.In this study, we found that the presence of the Ni/Al 2 O 3 catalyst leads to a decrease in conversions of CH 4 and CO 2 in comparison with plasma dry reforming in the absence of a catalyst. Similar observations have been reported in previous studies. Song et al.[START_REF] Song | [END_REF] investigated dry reforming of CH 4 in DBD using a pre-reduced 5 wt. % Ni/ -Al 2 O 3 in the absence of a diluent gas. The presence of the catalyst had little effect on the CH 4 conversions and on the H 2 and hydrocarbon selectivities. Kraus et al.[16] performed dry reforming of CH 4 in DBD using porous Al 2 O 3 foam with a 6 wt.% nickel coating. The yields of H 2 and hydrocarbons were unchanged by the presence of the Ni catalyst. However, CO yields were increased by 20-40 % compared to the results for an uncoated Al 2 O 3 foam. These findings


Introduction Developments and Plans for the Future for Ethnic and Racial Studies

Martin Bulmer

To cite this version: In part as a result of this increase we have decided, in consultation with our publishers, to move to producing 12 issues of Ethnic and Racial Studies per year in 2011. This reflects our commitment to ensuring that the journal is able to publish a wide range of high quality, cutting-edge articles which meet our stringent refereeing standards. It will also enable us to plan ahead in terms of including Special Issues as a regular part of this journal infuture. We now have a range of Special Issues in process which will take us to 2013 and beyond. We also held events linked to the journal at the International Sociological Association

Ethnic and Racial

Conference in Gothenburg (July 2010) and the American Sociological Association Conference in Atlanta (August 2010). Both events allowed us to publicise the work of the journal to broader audiences and to establish contact with the relevant research committees of the associations.

We have also worked closely with Routledge Journals to improve the scope and coverage of our Book Reviews section. We know that this is a section of the journal that many of our readers find of interest and we have moved to fully integrate the book reviews into our Scholar One electronic management process. This has allowed us to process books in a timely manner and to make sure that we publish reviews of the most recent books in our field as early as possible. It is our aim to continue to maintain and to broaden the international reach of this journal. This is more of a challenge in relation to books to be reviewed than it is for articles to be considered, but we continue to work to improve our coverage. Ethnic and Racial Studies is committed to international reach in the material which it publishes.

Following our practice last year, we are once again publishing in this issue, the last of the year, a list of all the referees that have helped us by looking at articles as part of our refereeing process. At the risk of stating the obvious, we are aware that we would not be able to maintain the high scholarly standards of the journal without your hard work. A number of our referees are members of our International Editorial Board, who number sixty-five scholars across eighteen countries. As the coverage of the journal expands, we rely also upon the advice and support of referees from a wide range of countries, disciplines and fields of research. To all who have acted as referees for ERS, a big thank you for your efforts and we look forward to your continued support in the future. Without this selfless voluntary interest in the articles which we received, we would not be able to publish the high quality material which it is the aim of the journal to disseminate.

  Martin Bulmer. Introduction Developments and Plans for the Future for Ethnic and Racial Studies. Ethnic and Racial Studies, 2010, 33 (10), pp.1689-1690. 10.1080/01419870.2010.512666. hal-for the Future for Ethnic and Racial Studies Introduction Developments and Plans for the Future for Ethnic and Racial Studies Martin Bulmer and John Solomos With this issue we complete Volume 33 of Ethnic and Racial Studies. This has been another successful year in the development of this journal, as reflected in the quality of the regular articles that we have published and in the articles included in the five Special Issues we have produced in 2010. The impact of the journal on the wider scholarly communities has been reflected in the increased Impact Factor we have been awarded in the ISI Social Science Citation Index for 2009, published in 2010. It is also evident in the increased volume of high quality submissions that we receive in the Editorial office from an increasing range of countries and research groupings. During both 2009 and 2010 we have seen significant increases in the submission of both regular and special issue articles to the journal.

uk Ethnic and Racial Studies

  Studies has been part of the evolution of scholarship and research on race, ethnicity, migration and and nationalism which continues to play an active role in professional activities that relate to the work of the journal. In May 2010 we held our Annual

	1
	2
	3
	4
	5
	6
	7
	8
	9
	10
	11
	12
	13
	14
	15
	16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 F o r P e e r R e v i e w O n l y
	2

Lecture at City University London, given by Ann Stoler from the New School for Social Research. This attracted a large audience composed of both established and younger scholars.

Page 1 of 3 URL: http://mc.manuscriptcentral.com/rers ethnic@surrey.ac.

uk Ethnic and Racial Studies

	Page 3 of 3	Page 2 of 3
	1
	2
	3
	4
	5
	6
	7
	8
	9 10	MARTIN BULMER
	11
	12	University of Surrey
	13
	14
	15
	16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 F JOHN SOLOMOS o P e e r R e v i e w O n l y r City University London
		3

URL: http://mc.manuscriptcentral.com/rers ethnic@surrey.ac.URL: http://mc.manuscriptcentral.com/rers ethnic@surrey.ac.

uk Ethnic and Racial Studies

	1
	2
	3
	4
	5
	6
	7
	8
	9
	10
	11
	12
	13
	14
	15
	16
	17
	18
	19
	20
	21
	22
	23
	24
	25
	26
	27
	28
	29
	30
	31
	32
	33
	34
	35
	36
	37
	38
	39
	40
	41
	42
	43
	44
	45
	46
	47
	48
	49
	50
	51
	52
	53
	54
	55
	56
	57
	58
	59
	60