The results illustrate how developers can tailor PtDAs using dynamic and interactive processes. We used a PtDA in development for patients with obstructive sleep apnea which is designed selleck chemicals to assist patients choice between three options: (i) Continuous Positive Airway Pressure (CPAP), a machine that pushes a stream of air through a mask into a patient’s nose or mouth to keep his throat and airway open; (ii) a Mandibular Advancement Splint (MAS), a type of mouthguard that helps to keep the patient’s throat open; and (iii) no treatment, or not adhering to using either CPAP or MAS. A recent review concluded that “the decision as to whether to use CPAP or MAS will likely depend on patient preference” [16]. We

invited members of an online panel to imagine they had been diagnosed with sleep apnea and were to use the PtDA to help their physician prescribe the most appropriate treatment option. They were told that adherence to these treatments was a particular concern, and so personal preferences were important to making treatment decisions. The PtDA broadly followed the IPDAS guidelines [17], explaining the condition, providing information about options and their

buy Veliparib characteristics (benefits, side-effects, costs, etc.) using probabilities and pictographs to describe baseline and incremental absolute risks where appropriate, a value clarification exercise, and a summary of information to help the patient deliberate on the decision along with an opportunity to select the preferred option. Given the hypothetical nature of the exercise, we did not include guidance

on next steps or on ways to discuss options with others, which would typically be included in a PtDA. Respondents were Clomifene randomized to three different versions of the PtDA: (1) conventional group, where the order of the information was pre-specified with benefits listed first, followed by side-effects, and then costs; (2) recency group, where information was ordered based on the results of a value clarification exercise, so that what a given respondent valued most was listed last; and (3) primacy group, where information again was ordered according to values, so that what a respondent valued most was listed first. The information contained in all three versions was identical, but the order in which information was displayed varied. We asked respondents questions about their preferred option and asked them to assign values to the attributes associated with each option. As a result we were able to determine the proportion of respondents who chose the option concordant with their own values. After completing consent, participants were informed that the survey was for improving an educational tool for patients with sleep apnea. They were then given information about sleep apnea so they could imagine that it would be like to have the condition. A simple test, referred to as a “catch trial”, was used to ensure they had paid attention to the information page.

Mais son enthousiasme a été un moteur puissant pour aller de l’avant. Nous nous souvenons tous de son humour, qui rend la vie plus belle ; de ses idées originales, surprenantes et pleines de bon sens ; de son humanité et son sens de l’empathie ; enfin, de son éternelle jeunesse : comment faisait-il ? Je l’ai rencontré quelques semaines avant son décès : malgré la maladie, j’ai retrouvé

chez lui cette énergie si contagieuse, si jeune que j’avais connue quelques années plus tôt. L’héritage du professeur Lequien n’est pas morose, mais il est exigeant. Nous continuerons dans la voie de l’innovation. Mais il est clair que, sur ce point, sa jeunesse d’esprit va nous manquer. L’annonce buy Alectinib du décès du professeur Lequien a profondément marqué ceux qui l’ont connu, comme en a témoigné le nombre de messages échangé à cette occasion. Un mail de Françoise Gonnaud résume admirablement le contenu de ces messages : « Un grand homme nous quitte et nous laisse “orphelins” :

orphelin de sa vision avec toujours une longueur d’avance, orphelin de sa belle capacité à faire évoluer notre Société de médecine périnatale, orphelin de tout ce que chacun a retenu de ce qu’il représentait. Alors je fais un vœu pour nous tous : comme personne ne peut rassembler en lui seul toutes ses qualités extraordinaires (comme il le faisait si bien), le meilleur hommage que nous pourrions lui rendre serait de poursuivre ce chemin en maintenant ouverte toutes les portes qu’il a osé entrouvrir. Que chacun s’approprie une petite mission pour faire vivre cet héritage incontestable… Je veux bien prendre une petite partie : comme essayer d’oser dire tout Apitolisib cost haut ce que chacun peut penser tout bas… mais pas toute seule ! Il le faisait si bien dans le respect de chacun mais pour faire progresser le groupe “
“Erratum à l’article « Du PELVIS au LUMBAR syndrome : à propos de 2 cas » paru dans le numéro (2012 ;19 (1) : ADAMTS5 55–8), des Archives de Pédiatrie. L’auteur, Natacha Kadlub, nous a signalé qu’elle souhaitait ajouter l’auteur « G. Audry

du service de chirurgie viscérale pédiatrique, faculté de médecine Pierre-et-Marie-Curie ; Paris 6, hôpital d’enfant Armand-Trousseau, AP–HP, 26, rue du Docteur-Arnold-Netter, 75571 Paris cedex 12, France ». Ci-après la liste des auteurs rectifiée : F. Fradea,b, N. Kadluba,b*, V. Souprea,b, S. Cassiera,b, G. Audryc, M.-P. Vazqueza,b, A. Picarda,b a Service de chirurgie maxillo-faciale et plastique, faculté de médecine Pierre-et-Marie-Curie Paris 6, hôpital d’enfant Armand-Trousseau, centre hospitalier STARTT, AP–HP, 26, rue du Docteur-Arnold-Netter, 75571 Paris cedex 12, France b Inserm UMRS 872, centre de recherche des cordeliers, rue de l’École-de-médecine, 75006 Paris, France c Service de chirurgie viscérale pédiatrique, faculté de médecine Pierre-et-Marie-Curie Paris 6, hôpital d’enfant Armand-Trousseau, AP–HP, 26, rue du Docteur-Arnold-Netter, 75571 Paris cedex 12, France * Auteur correspondant : email : natacha.kadlub@trs.

The protein and mRNA levels of TNF-α, IFN-γ, IL-1β, IL-17A, TLR4,

TRAF6 and NF-κB significantly increased after DSS administration. MSCs transplantation markedly ameliorated the pathology of colon and liver by reduction of LPS level, and proteins and mRNA expressions of TNF-α, IFN-γ, IL-1β, IL-17A, EPZ015666 TLR4, TRAF6 and NF-κB as well. Our results reveal that MSCs may be a novel therapeutic drug for the treatment of chronic colitis-associated cholangitis, which correlated to downregulating the LPS/TLR4 signaling pathway. “
“The role of IL-10-producing B cells in inflammatory bowel diseases (IBD) is poorly understood. Several studies suggested that B cell depletion might lead to developing human colitis (IBD 2007, Gut 2008). We hypothesize that intestinal B cells contribute to mucosal homeostasis and protection against IBD through IL-10 secretion. Wild-type (WT) or IL-10−/− splenic CD4+ T cells were co-transferred with purified splenic B cells from WT or IL-10−/− mice into Rag2−/−IL-10−/− (DKO) mice. 6 weeks after co-transfer, these mice were evaluated for colitis severity by histology (0: normal, 12: severe inflammation), cytokine secretion by colonic tissue explant (gut culture) and mesenteric lymph nodes (MLN) (MLN culture), and Foxp3 expression in MLN CD4+ T cells.

To investigate buy APO866 suppressive mechanisms of B cells on bacteria-activated Urease differentiation of naïve T cells in vitro, WT or IL-10−/− B cells were co-cultured with CD25−CD4+ T cells from IL-10+/EGFP reporter mice and IL-10−/− antigen-presenting cells (APC) stimulated by cecal bacterial lysates (CBL). IL-10, IFNγ and IL-17a supernatant levels were measured by ELISA and IFNγ, IL-17a, Foxp3 and GFP expression

were assessed by FACS. In vivo, WT CD4+ T cell recipient DKO mice that received co-transferred WT B cells developed less severe colitis than those receiving either IL-10−/− B cells or no B cells (histology 4.3±1.0, 7.2±1.1 and 7.6±0.7, p<0.02). Gut and MLN culture demonstrated that either spontaneous or bacteria-induced IFNγ and IL-17a secretion was significantly lower and IL-10 levels were higher in DKO mice that received WT B cells than those receiving IL-10−/− B cells or no B cells. MLN CD4+ T cell Foxp3 expression was induced by co-transferring either WT B cells (10.9±1.0%, p<0.05) or IL-10−/− B cells (11.6±0.8%, p<0.05), compared to animals without B cells (7.4±1.2%). In contrast, all DKO mice with transferred IL-10−/−CD4+ T cells developed severe colitis with no evidence of suppression by WT or IL-10−/− B cells. In vitro, WT but not IL-10−/− B cells suppressed IFNγ and IL-17a production by CBL-stimulated CD4+ T cells. FACS demonstrated that % of either CBL-stimulated IL-17a+ or IFNγ+ CD4+ T cells were significantly lower when co-cultured with WT but not IL-10−/− B cells.

Moreover, the generation time of the final product (ceramide 1-phosphate), is compatible with the cellular early response (before 30 min) observed

for Calcium influx. Finally, the activity of recombinant brown spider phospholipase-D on B16-F10 cells was further confirmed by its ability to stimulate cell Roxadustat proliferation in a concentration and time-dependent manner. Additionally, the increases in the cell proliferation rate in B16-F10 cells following LiRecDT1 exposure were higher when the cells were incubated in the presence of exogenous sphingomyelin (which was, as reported, a good substrate for recombinant phospholipase-D). A putative explanation for this event is that exogenous sphingomyelin increases the concentration and accessibility of enzyme substrates, generating bioactive lipid mediators following treatment with recombinant brown spider proteins (such as ceramide 1-phosphate or interconvertible lipids such as ceramide, sphingosine and sphingosine

HKI-272 1-phosphate), compared to offering lipid substrates organized in the lipid bilayer of cell membranes. The results described herein indicated that B16-F10 melanoma cells subjected to exogenous treatment with a recombinant phospholipase-D from brown spider venom (LiRecDT1) bound phospholipase-D at the cell surface, did not suffer changes in viability, ID-8 experienced metabolism of their phospholipids by the enzyme, generated metabolically bioactive lipids, triggered Calcium mobilization inside the cytosol, and had their proliferation stimulated, especially in the presence of exogenous sphingomyelin.

The data indicated that venom phospholipase-D, which is also referred to as “dermonecrotic toxin” because it is directly involved on gangrenous and necrotic loxoscelism due to generating bioactive lipids such as lysophosphatidic acid and/or ceramide 1-phosphate, can also modulate membrane phospholipid metabolism, regulate tumor cell proliferation, and modulate the cytosolic Calcium influx, opening the possibility of using this enzyme as a novel biotool in studies addressing phospholipid and calcium metabolism. This work was supported by grants from CAPES, CNPq, Fundação Araucária-PR and the Secretaria de Estado de Ciência, Tecnologia e Ensino Superior do Paraná, Brazil. “
“TTX, a specific blocker of voltage-gated sodium channels of excitable membranes of muscle and nerve tissues (Colquhon et al., 1972; Narahashi, 2001), and one of the most potent neurotoxins, was long believed to occur exclusively in pufferfish.

What all of these studies and broader more integrative studies confirm is the importance of considering community livelihoods, particularly when “no-take” MPAs are employed, as well as governance and management for the success of MPAs [22], [45], [46] and [47]. The Bleomycin sustainable livelihoods literatures provided a frame of reference for our research and analysis. Sustainable livelihoods frameworks proposed by Carney [33], DFID [72], Scoones [34] and Ellis [35] suggest that there

are a number of micro to macro-level contextual factors – including trends and shocks as well as policies, institutions, and processes – that transform and mediate access to assets and have impacts on livelihood strategies or portfolios and the resultant socio-economic and environmental outcomes (Fig. 1). Central to the sustainable livelihoods frameworks are a number of capitals or assets that are the platform for livelihood strategies. These assets include natural, social, human, physical, financial,

cultural, and political capitals – definitions of each provided in Table 2. In the context of this framework, a marine protected area can be seen as a social institution that is comprised of a series of laws, policies and processes that are enacted by various levels of government (as well as private sector and civil society actors) through applied governance and management. It has been suggested elsewhere that the SL framework is useful as a tool for analyzing the impacts of protected areas on livelihood outcomes and assets learn more and the role of protected area policies, institutions, and processes (i.e., management and governance) in producing these outcomes with the ultimate Methane monooxygenase goal of improving conservation practice [73] and [74]. Since the sustainable livelihoods literatures provided little guidance on management and governance, literatures on protected areas governance [23] and [36] and management

[22] and [37] were also used when analyzing results of this study. Good governance is promoted through legitimacy, transparency, accountability, inclusiveness or participation, fairness or equity, integration or coordination, capability, and adaptability. Effective MPA management requires adequate capacity and resources, effective communication of rules and regulations (e.g., boundaries), extensive programs of education and outreach, participatory processes of creation and management structures, consideration of the values of all stakeholders, relationships built on trust, coordination with other management institutions, integration of scientific and traditional knowledge, and mechanisms for conflict resolution and to ensure transparency and accountability. Effective management also relies on monitoring, evaluation and adaptation of actions based on a management plan. Seven communities, situated near 4 different MPAs, were chosen for the purposes of this study.

Critically, between these extremes lies equi-modal cortex in the inferior temporal and fusiform gyri that responds similarly across modalities and presumably BMS-354825 solubility dmso codes transmodal structure. In summary, the process of extracting meaning from our experience with objects involves the fusion of complex sets of information from sensory inputs, motor programmes and verbal experience. We have demonstrated that one key aspect of

this process, the integration of individual features into coherent concepts, depends critically on the ATLs. We are indebted to the patients and their carers for their generous assistance with this study. We thank Prof. Alistair Burns, Prof. Roy Jones and Dr. Roland Zahn for referring patients to us. The research was supported by an MRC Programme Grant (MR/J004146/1), an NIHR Senior Investigator Award to M.A.L.R., an MMHSCT Stepping Stone Award to P.H. and a Wellcome Trust Institutional Strategic Support Fund (ISSF) award (097820) to the University of Manchester. “
“Face recognition is an important cognitive skill that most people take for granted, yet it depends on a complex set of cognitive and neural processes (Bruce and Young, 1986 and Haxby et al., 2000). In some individuals this process can be selectively disrupted, resulting in a condition termed “prosopagnosia” or “face-blindness”.

While prosopagnosia can be acquired following brain injury (e.g., Damasio, Damasio, & Van Hoesen, 1982), many this website more individuals simply fail to develop normal face recognition Coproporphyrinogen III oxidase abilities (e.g., Bate et al., 2009, Bate et al., 2008 and Behrmann and Avidan, 2005; Bentin, Deouell, & Soroker, 1999; Duchaine et al., 2007, Duchaine and

Nakayama, 2006, Jones and Tranel, 2001 and Schmalzl et al., 2008). The latter form of the disorder has been termed ‘developmental prosopagnosia’ (DP; but for a discussion of terminology see Susilo & Duchaine, 2013), and has been attributed to a failure to develop the visual recognition mechanisms necessary for successful face recognition, despite intact low-level visual and intellectual functions. Interestingly, there also appears to be a genetic component to the disorder in at least some individuals (Duchaine et al., 2007 and Grueter et al., 2007). In the last decade it has become increasingly clear that DP represents a significant clinical disorder, with recent reports suggesting that two percent of the population have the condition (Bowles et al., 2009 and Kennerknecht et al., 2006). Although many studies have investigated the cognitive, neural and genetic basis of DP, little attention has been directed towards improving face recognition in these individuals. While some researchers have attempted to remedy face processing deficits using extensive visual training programmes (e.g., DeGutis et al., 2007 and Schmalzl et al., 2008), recent evidence suggests that an alternative methodology warrants investigation.

Additionally, these lower-level species are commonly associated with high rates of population turnover and an unstable abundance [6]. The SBSTTA stressed the importance of MTI as a biodiversity indicator, claiming that MTI is, “considered a particularly effective indicator to assess sustainability of fishing and the integrity of marine ecosystems” [6]. For this

reason, researchers affiliated with the CBD agree that policy decisions relating to the management of a species must include consideration of trophically-linked species [6]. Since the 2006 agreement by the Conference of the Parties to the CBD, several states obligated to the agreement have undergone national reviews of the application of MTI. These analyses discuss the possible incorporation of

MTI into national fisheries management decisions. Much of the current research Dasatinib manufacturer has been centered in the European Union (EU), likely because the EU was among the earliest groups to adopt CBD indicators for biodiversity monitoring. In the summer of 2004, the EU Environment Council adopted 15 of the biodiversity indicators highlighted by the CBD, including MTI [17]. By 2005, the indicators were also adopted by the Pan-European Biological and Landscape Diversity Strategy selleck products [17]. The incorporation of MTI as a measure of diversity into two landmark Interleukin-2 receptor agreements in the European sphere represents a strong push toward sustainability on the European continent. In response to the continental push for MTI to be incorporated into fishery management decisions, pilot studies were performed by the British and Dutch in 2008 and 2007, respectively. In the United Kingdom (UK), significant effort has gone into the research and implementation of MTI into national policy decisions. The UK Biodiversity Partnership Standing Committee agreed upon 18 promising biodiversity indicators requiring additional follow-up to implement. Among the proposed indicators was MTI. In a 2008 report on the feasibility and accuracy of using MTI to estimate

ecosystem health in UK territorial waters, scientists concluded that the data needed to compute MTI was not available at a small-scale necessary to accurately predict MTI for the UK. Ultimately, the UK Committee recommended against the incorporation of an MTI indicator into management regimes, citing that, “data may not be representative of all trophic levels in UK waters, especially regionally” [18]. Similarly, a 2007 Dutch report was commissioned to examine the possibility of using MTI as an indicator for ecosystem health in the Netherlands territorial seas. The report identified MTI as offering, “the possibility to encapsulate data on fisheries landings in one figure, making changes in fisheries behavior visible in one glance” [17].

Two authors (K.-V.C., C.-Y.H.) independently evaluated all articles eligible for inclusion. The data extracted from the selected studies included patient characteristics, information on PRP administration, and details of outcome measurements. The Jadad scale was used to assess the quality of the randomized controlled trials. The aggregate scores ranged from 0 to 5 points. Trials with scores <3 were assumed to have a lower methodological quality.15 Prospective follow-up and quasi-experimental www.selleckchem.com/products/Bleomycin-sulfate.html studies were evaluated by using the Newcastle-Ottawa Scale to assess the quality of selection, comparability, exposure, and outcome. The maximum scores observed

were 9 points, and total scores <4 points were considered low in quality.16 Discrepancies between the 2 independent evaluations for potential articles were resolved through discussion and consensus. Data were extracted from 3 points at or closest to the 2nd, 6th, and 12th months

after the interventions. Effect sizes were estimated from functional knee joint scales and applied to compare the results across studies or between different therapeutic approaches. SP600125 If more than 1 functional scale was available for a study, we selected only 1 measurement according to the order of IKDC, KOOS, and then WOMAC. Since some studies had multiple treatment arms, we treated each arm as a separate data set for analysis. To evaluate the effectiveness of PRP treatment, compared with the pretreatment condition, Methane monooxygenase we used the standardized mean difference between the

baseline and status after therapy. Data were derived from the ratio of the difference between baseline and posttreatment functional scores to the SD of the pooled results. Positive and negative values of the effect sizes indicated a functional improvement and decline, respectively. For cases in which the functional score SD was deficient, the value was computed from the P value of the corresponding hypothesis testing. The pooled SD resulted from the square root [(participant numbers in baseline − 1)*(SD of scores in baseline)2 + (participant numbers after treatment − 1)*(SD of scores after treatment)2]/[(participant numbers in baseline − 1) + (participant numbers after treatment − 1)]. 16 and 17 Because the pooled SD was calculated based on the rule of intention to treat, the dropout rate was not considered, and the participant numbers remained unchanged between the baseline and posttreatment data sets. The effect sizes were pooled by using a random-effect model and were represented by a point estimate with a 95% confidence interval (CI). Regarding the comparison with the baseline condition, an advantage of PRP referred to a positive summed effect size with a 95% CI above a zero value.

Insbesondere Haare wurden in Studien zum Zusammenhang zwischen der Exposition und neuropsychologischen Effekten bei Kindern als Matrizes für die Bestimmung von Mn und anderen Metallen verwendet [17], [44] and [100].

Die ermittelten Konzentrationen waren jedoch ∼ 4- bis 70-mal höher als die bei einer Studie von Eastman et al. ermittelten [101], für die ein mehrstufiges Verfahren zur Reinigung der Haare vor der Bestimmung von Mn (und Pb, Cr, Cu) entwickelt worden war. Wenn Haare zur Bestimmung von Mn verwendet werden, ist deren Reinigung vor der Analyse unerlässlich. Trotzdem bleiben Haare eine unsichere Matrix für das Biomonitoring, da es äußerst schwierig ist, zwischen exogenem und metabolisch KU-57788 manufacturer inkorporiertem Mn zu unterscheiden, insbesondere da die Konzentrationen nach einem gewissen Zeitraum wieder zu normalen Werten zurückkehren [7]. Scans am

lebenden Gehirn mithilfe des MRT sind eine weitere vielversprechende Methode, die möglicherweise zur Diagnose von Mn-Neurotoxizität und Mn-Überexpression verwendet werden kann [4] and [7]. In einer Querschnittstudie untersuchten Jiang et al. [102] 18 Mn-exponierte Beschäftigte, von denen 13 hoch exponierte Schmelzer (Bereich der Exposition 0,31-2,93 mg/m3), 5 Mitarbeiter der Stromversorgungsabteilung derselben Fabrik (Bereich 0,23-0,77 mg/m3) und 9 Büroangestellte einer anderen Firma waren, die als Kontrollpersonen dienten (Bereich Sotrastaurin ic50 0-0,01 mg/m3). Die MRT-Daten

zeigten einen durchschnittlichen Anstieg des Pallidum-Index (PI) von 7,4 % (p < 0,05) und 16,1 % (p < 0,01) in der Gruppe der Arbeiter mit niedriger (n = 5) bzw. hoher (n = 18) Exposition, acetylcholine jeweils im Vergleich zur Kontrollgruppe. Klinische Symptome und Anzeichen von Manganismus wurden allerdings nicht beobachtet. Darüber hinaus wiesen 14 der 18 Mn-exponierte Mitarbeiter (78 %) erhöhte PI-Werte auf, wobei der Anteil unter den stark exponierten Arbeitern noch höher war (85 %). Der Mn-Spiegel im Vollblut, im Plasma und in den Erythrozyten wurde ebenfalls bestimmt. Bei den exponierten Arbeitern zeigten die PI-Werte eine signifikante (positive) Korrelation mit dem Mn-Gehalt der Erythrozyten. Die Autoren folgerten, dass T1-gewichtete MRT-Scans ein geeigneter Indikator für eine kürzliche Exposition von aktiven Beschäftigten gegenüber Mn in der Luft sein könnten, jedoch wahrscheinlich nicht sensitiv genug für Patienten sind, die aus dem belasteten Bereich entfernt worden sind. Darüber hinaus schlugen die Autoren vor, dass Erythrozyten nützlicher für das Mn-Biomonitoring sein könnten als Plasma oder Serum, da die Mn-Transporter TfR und DMT1 in Erythrozyten nachgewiesen wurden. Trotzdem bildet der MRT-Ansatz allein keine anwendbare Methode für ein aussagekräftiges Biomonitoring beim Menschen (HBM). Daher nahmen Cowan et al. eine intensive Evaluation von Matrizes für ein Mn-Biomonitoring vor [103].

120 However, the treatment duration employed in this study (5 days every 28 days for 9–12 cycles) may have been suboptimal in a population of patients with chronic infection. 121 Ongoing and future trials will inform us if inhaled antibiotics are a useful therapeutic option in the prevention of exacerbations

of COPD. Acute, efficacious antibiotic BGB324 treatment is the mainstay in the management of patients with severe COPD and symptomatic exacerbations that include at least 2 of the 3 cardinal symptoms (increased sputum purulence, volume and increased dyspnoea; Anthonisen type I or II exacerbations). Although such treatment is associated with clinical benefit, treatment failure and relapse rates may HIF-1 pathway be high in patients with the frequent exacerbator phenotype. Failure may be related to inadequate antibiotic efficacy through incomplete resolution of the initial exacerbation and persistent bacterial infection.23, 24, 25 and 26 These factors have led to recommendations for a stratified approach to antibiotic therapy based on patient risk factors.15 Patients at greatest risk for poorer outcome (i.e. those with complicated COPD) are likely to derive greatest benefit from early treatment with the most potent antibiotic therapy, such as amoxicillin/clavulanate and respiratory fluoroquinolones which

have a broad spectrum of activity against likely pathogens.28, 122, 123 and 124 The use of the most efficacious antibiotics in patients

with risk factors may be crucial in preventing relapses or delaying subsequent exacerbations which appear to cluster in time, and if the exacerbation O-methylated flavonoid is poorly controlled there is a high risk of the next episode occurring within a few weeks.30 A significant relationship exists between bacterial eradication at the end of antibiotic treatment and no relapse in the following eight weeks.28 Studies conducted in the last 20 years suggest that long-term or intermittent antibiotic therapy may have a beneficial effect on the outcome of COPD patients and may improve quality of life by reducing exacerbation frequency and hospitalisations for exacerbations, or by extending time to next exacerbation. The mechanisms underlying such improvements are unclear. It is possible that the benefit of long-term antibiotic treatment may be due to a reduction in the frequency of exacerbations due to eradication of colonising potentially pathogenic bacteria and/or reduction in chronic airway inflammation,37 though the evidence supporting such a hypothesis is limited. While macrolides are known to have both antibacterial and anti-inflammatory effects, it is unknown to what degree these actions are responsible for their efficacy when used for the treatment of chronic respiratory conditions.